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Amiresmaili S, Rajizadeh MA, Jafari E, Bejeshk MA, Salimi F, Moslemizadeh A, Najafipour H. Myrtenol ameliorates inflammatory, oxidative, apoptotic, and hyperplasic effects of urethane-induced atypical adenomatous hyperplasia in the rat lung. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1785-1797. [PMID: 39177787 DOI: 10.1007/s00210-024-03375-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 08/12/2024] [Indexed: 08/24/2024]
Abstract
Lung atypical adenomatous hyperplasia (AAH) is a forerunner of pulmonary adenocarcinoma. The drugs being utilized in the remediation of this type of hyperplasia have some adverse impacts. The present research focused on the potential anti-hyperplasia effect of myrtenol, an herbal terpenoid, on urethane-induced lung AAH in rats. Rats were injected with urethane (1.5 g/kg) thrice at 48 h intervals, and 20 weeks later, the animals were treated with 50 mg/kg myrtenol intraperitoneally once a day for 1 week. The ELISA method was used to measure inflammatory cytokines and oxidative parameters in the lung tissue and bronchoalveolar lavage fluid (BALF). The expression of NFκB and apoptotic/antiapoptotic factors (P53/Bcl-2) was evaluated by western blot and immunohistochemistry, respectively. H&E staining was performed for histopathological investigation. Histopathology confirmed the anti-hyperplasia effect of myrtenol, which was evidenced by the reduction of bronchoalveolar wall thickness and inflammation score. It also decreased hyperplasia progression by reducing Bcl-2, IL-10, p53, and Ki67. Compared with the urethane group, myrtenol normalized the activity of the oxidative stress markers malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Moreover, it showed an anti-inflammatory effect by decreasing lung and BALF IL-1β levels and NFκB expression. Myrtenol may have a promising effect on lung cancer treatment by counteracting lung hyperplasia via modulation of inflammation, oxidative stress, and apoptosis.
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Affiliation(s)
| | - Mohammad Amin Rajizadeh
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Elham Jafari
- Department of Pathology, Pathology and Stem Cell Research Center, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Abbas Bejeshk
- Department of Physiology, Bam University of Medical Sciences, Bam, Iran
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Fouzieh Salimi
- Department of Clinical Biochemistry, Medical Faculty, and Endocrinology and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Amirhossein Moslemizadeh
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Najafipour
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
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Kim SJ, Kim E, Rim KT. Non-invasive quantification of cell-free DNA mutations in plasma during lung tumor progression in mice. Cancer Biomark 2017; 20:477-485. [PMID: 28946552 DOI: 10.3233/cbm-170303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Testing carcinogenicity caused by chemicals requires a noninvasive tool that can be used before autopsy because autopsy takes a long time. We investigated whether non-small cell lung cancer related gene mutations could be detected in cell-free DNA in plasma by Insight OncoTM next-generation sequencing, which is a fast and sensitive method. Adenoma formation was confirmed in urethane-injected 17-week-old mice. Seven single nucleotide polymorphisms, such as Cdkn2a and Vegfa, were selected. Mutant-enriched Insight OncoTM NGS and normal NGS were performed on genomic DNA. The results demonstrate that Insight OncoTM NGS detected Cdkn2a and Vegfa SNPs at 0.05%. The sensitivity of Insight OncoTM NGS was twice higher than that of normal NGS. In this analysis, the Cdkn2a gene mutation was detected not only in two genomic DNA samples of lung tissue from the 11th week of urethane injection but also in two cell-free DNA samples. In addition, the Vegfa gene mutation was detected not only in three genomic DNA samples of lung tissue of injection but also in one cell-free DNA sample, showing 33% concordance. Our results confirm that Insight OncoTM NGS is a rapid and sensitive detection method that enables lung cancer-associated gene mutations to be detected in cell-free DNA before the end of the carcinogenicity test.
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Affiliation(s)
- Soo-Jin Kim
- Chemicals Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, Daejeon 34122, Korea.,Department of Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Korea
| | - Eunhee Kim
- Department of Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Korea
| | - Kyung-Taek Rim
- Chemicals Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, Daejeon 34122, Korea
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Preclinical Murine Models for Lung Cancer: Clinical Trial Applications. BIOMED RESEARCH INTERNATIONAL 2015; 2015:621324. [PMID: 26064932 PMCID: PMC4433653 DOI: 10.1155/2015/621324] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Accepted: 11/24/2014] [Indexed: 12/18/2022]
Abstract
Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.
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Wan Kamarul Zaman WS, Makpol S, Sathapan S, Chua KH. Long-termin vitroexpansion of human adipose-derived stem cells showed low risk of tumourigenicity. J Tissue Eng Regen Med 2012; 8:67-76. [DOI: 10.1002/term.1501] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Revised: 01/20/2012] [Accepted: 01/25/2012] [Indexed: 11/11/2022]
Affiliation(s)
| | - Suzana Makpol
- Department of Biochemistry, Faculty of Medicine; Universiti Kebangsaan Malaysia; Kuala Lumpur Malaysia
| | | | - Kien Hui Chua
- Department of Physiology, Faculty of Medicine; Universiti Kebangsaan Malaysia; Kuala Lumpur Malaysia
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Svec J, Ergang P, Mandys V, Kment M, Pácha J. Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models. Int J Exp Pathol 2010; 91:44-53. [PMID: 20096072 DOI: 10.1111/j.1365-2613.2009.00698.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Elevated levels of survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and the regulatory factors c-MYB and Tcf-4 are often found in human cancers including colorectal cancer (CRC) and have been implicated in the development and progression of tumorigenesis. The aim of this study was to determine the expression of these genes in mouse models of sporadic and colitis-associated CRC. To address these issues, we used qRT-PCR approach to determine changes in gene expression patterns of neoplastic cells (high-grade dysplasia/intramucosal carcinoma) and surrounding normal epithelial cells in A/J and ICR mouse strains using laser microdissection. Both strains were injected with azoxymethane and ICR mice were also given drinking water that contained 2% dextran sodium sulphate. In both sporadic (A/J mice) and colitis-associated (ICR mice) models of CRC, the levels of TERT mRNA, COX-2 mRNA and Tcf-4 mRNA were higher in neoplastic cells than in surrounding normal epithelial cells. In contrast, survivin mRNA was upregulated only in neoplastic cells from A/J mice and ILK mRNA was upregulated only in neoplastic cells from ICR mice. However, the expression of iNOS mRNA was similar in normal and neoplastic cells in both models and c-MYB mRNA was actually downregulated in neoplastic cells compared with normal cells in both models. These findings suggest that the genetic background and/or the molecular mechanisms of tumorigenesis associated with genotoxic insults and colonic inflammation influence the gene expression of mTERT, COX-2, Tcf-4, c-MYB, ILK and survivin in colon epithelial neoplasia.
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Affiliation(s)
- Jirí Svec
- Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic
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Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway. Neoplasia 2007; 9:840-52. [PMID: 17971904 DOI: 10.1593/neo.07517] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2007] [Revised: 08/10/2007] [Accepted: 08/14/2007] [Indexed: 12/13/2022] Open
Abstract
The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers and genetic alterations. We analyzed markers of DNA damage response (DDR), proliferative stress, and telomeric stress: gamma-H2AX, p16, p53, and TERT. Lung cancer-related epigenetic and genetic alterations, including promoter hypermethylation status of p16(CDKN2A), APC, CDH13, Rassf1, and Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, and c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase and p53 induction. p16 was also induced in early tumorigenic progression and was inactivated in bronchiolar dysplasias and tumors. Remarkably, lack of mutations of Ras and epidermal growth factor receptor, and a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A), CDH13, and APC, but not in Rassf1 and Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.
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Shin JW, Lee SH, Park ES. Expression of Caspase 3, Survivin, and p53 Protein in Urethane Induced Mouse Lung Carcinogenesis. Tuberc Respir Dis (Seoul) 2007. [DOI: 10.4046/trd.2007.63.3.251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Jong Wook Shin
- Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung Ang University College of Medicine, Seoul, Korea
| | - Soo Hwan Lee
- Department of Pathology, Chung Ang University College of Medicine, Seoul, Korea
| | - Eon Sub Park
- Department of Pathology, Chung Ang University College of Medicine, Seoul, Korea
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Wakamatsu N, Devereux TR, Hong HHL, Sills RC. Overview of the molecular carcinogenesis of mouse lung tumor models of human lung cancer. Toxicol Pathol 2007; 35:75-80. [PMID: 17325975 PMCID: PMC2094362 DOI: 10.1080/01926230601059993] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Lung cancer is the leading cause of cancer death worldwide, and the need to develop better diagnostic techniques and therapies is urgent. Mouse models have been utilized for studying carcinogenesis of human lung cancers, and many of the major genetic alterations detected in human lung cancers have also been identified in mouse lung tumors. The importance of mouse models for understanding human lung carcinogenic processes and in developing early diagnostic techniques, preventive measures and therapies cannot be overstated. In this report, the major known molecular alterations in lung tumorigenesis of mice are reviewed and compared to those in humans.
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Affiliation(s)
- Nobuko Wakamatsu
- Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
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Takakura M, Kyo S, Inoue M, Wright WE, Shay JW. Function of AP-1 in transcription of the telomerase reverse transcriptase gene (TERT) in human and mouse cells. Mol Cell Biol 2005; 25:8037-43. [PMID: 16135795 PMCID: PMC1234330 DOI: 10.1128/mcb.25.18.8037-8043.2005] [Citation(s) in RCA: 93] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The transcriptional regulation of the human telomerase catalytic subunit (hTERT) plays a critical role in telomerase activity. Approximately 200 bp of the proximal core promoter is responsible for basic hTERT expression; however, the function of the distal regulatory elements remains unclear. The transcription factor activator protein 1 (AP-1) is involved in cellular proliferation, differentiation, carcinogenesis, and apoptosis and is expressed broadly in both cancer and normal cells. There are several putative AP-1 sites in the hTERT promoter, but their functions are unknown. The present study examined the regulatory role of AP-1 in hTERT gene transcription. Overexpression of AP-1 leads to transcriptional suppression of hTERT in cancer cells. The combination of c-Fos and c-Jun or c-Fos and JunD strongly suppresses hTERT promoter activity in transient-expression analyses. The hTERT promoter region between -2000 and -378 is responsible for this function. Gel shift and supershift analyses, as well as ChIP, show binding of JunD and c-Jun on two putative AP-1 sites within this region. Mutations in the AP-1 binding sites rescued suppressions caused by AP-1, suggesting this is a direct regulation of the hTERT promoter. In contrast, there was no effect on mTERT expression or mTERT promoter activity by AP-1 overexpression in mouse fibroblasts. The species-specific function of AP-1 in TERT expression may in part help explain the difference in telomerase activity between normal human and mouse cells.
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Affiliation(s)
- Masahiro Takakura
- Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9039, USA
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Winters CJ, Mikhailova MV, Andreoli TE. Cl- channels in basolateral TAL membranes. XIX. Cytosolic Cl- regulates mmCIC-Ka and mcCIC-Ka channels. J Membr Biol 2004; 195:73-84. [PMID: 14692447 DOI: 10.1007/s00232-003-2046-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
We evaluated the effects of culturing mouse MTAL cells under conditions that suppressed steady-state cytosolic Cl- on chloride channels fused into bilayers from basolateral vesicles of cultured MTAL cells. We used two agents to suppress Cl- entry: 10(-6) M PGE2 and 10(-4) M bumetanide. Basolateral Cl- channels from control cultured MTAL cells exhibited the signature characteristics of mmCIC-Ka channels: increased open-time probability (Po) either by raising cytosolic-face [Cl-] or, at 2 mM cytosolic Cl-, by adding (ATP + PKA), and first-order conductance kinetics. Either 10(-6) M PGE2 or 10(-4) M bumetanide in culture media reduced steady-state MTAL cytosolic Cl-. Chloride channels from these cells exhibited characteristics unique to CTAL mcCIC-Ka channels, namely: no augmentation of Po either by raising cytosolic Cl- or with cytosolic (ATP + PKA), and multi-ion occupancy. Semi-quantitative RT-PCR and real-time quantitative PCR showed that culturing MTAL cells with 10(-6) M PGE2 or 10(-4) M bumetanide reduced mRNA levels encoding mmCIC-Ka but not mRNA levels encoding mcCIC-Ka. However, when MTAL cells were cultured under control conditions, and then pre-incubated for 60 minutes with 10(-4) M bumetanide, cytosolic Cl- fell acutely but Cl- channels exhibited characteristics of mmCIC-Ka channels. Thus PGE2 and bumetanide, both of which lower steady-state MTAL cytosolic Cl- concentrations, inhibit either the transcriptional and/or the translational processes for mmCIC-Ka synthesis.
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Affiliation(s)
- C J Winters
- Division of Nephrology, Department of Internal Medicine, University of Arkansas College of Medicine, and The Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA
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Altavilla G, Caputo A, Trabanelli C, Brocca Cofano E, Sabbioni S, Menegatti MA, Barbanti-Brodano G, Corallini A. Prevalence of liver tumours in HIV-1 tat-transgenic mice treated with urethane. Eur J Cancer 2004; 40:275-83. [PMID: 14728943 DOI: 10.1016/j.ejca.2003.08.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The human immunodeficiency virus type 1 (HIV-1) Tat protein stimulates cell proliferation, inhibits apoptosis, displays angiogenic functions and is believed to be involved in the pathogenesis of Kaposi's sarcoma (KS) and other tumours arising in AIDS patients. Tat-transgenic (TT) mice, which constitutively express Tat in all tissues and organs, may therefore be predisposed to tumorigenesis. To test this hypothesis, we treated TT mice with urethane, a general carcinogen inducing tumours of various organs. The results indicate that, after injection of urethane, the incidence of lung tumours and lymphomas is not significantly different in the TT and control (CC) mice, whereas liver preneoplastic lesions and tumours show a significantly greater incidence in TT than in CC mice. This remarkable carcinogenic effect of urethane for the liver may be due to a tat-induced predisposition, manifested as a liver cell dysplasia (LCD), spontaneously affecting most of the TT mice. LCD may exert a promoting effect by stimulating proliferation of cell clones initiated by the mutagenic effect of urethane. In addition, LCD, which is associated with aneuploidy and chromosome instability, may enhance the progression to malignancy of the preneoplastic lesions induced by urethane. Interestingly, a significantly greater incidence of vascular ectasias and haemangiomas was detected in the liver of urethane-treated TT mice, most likely due to the marked angiogenic properties of Tat. This study suggests a role for Tat in the promotion and progression of tumours initiated by exogenous and endogenous carcinogens in HIV-1-infected patients, thereby contributing to the tumorigenesis in the course of AIDS.
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Affiliation(s)
- G Altavilla
- Institute of Pathologic Anatomy and Histology, University of Padova, I-35100 Padova, Italy
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Piao YF, Shi Y, Gao PJ. Inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell proliferation. World J Gastroenterol 2003; 9:2117-20. [PMID: 12970919 PMCID: PMC4656687 DOI: 10.3748/wjg.v9.i9.2117] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell line SMMC-7721 and to explore the mechanism of its effect.
METHODS: SMMC-7721 cells were divided into two groups, one treated with all-trans retinoic acid (ATRA) for 5 days and the other as a control group. Light microscope and electron microscope were used to observe the morphological changes. Telomerase activity was analyzed with silver-stained telomere repeated assay protocal (TRAP). Expression of Caspase-3 was demonstrated with western blot.
RESULTS: ATRA-treated cells showed differentiation features including small and pyknotic nuclei, densely stained chromatin and fewer microvilli. Besides, ATRA could inhibit the activity of telomerase, promote the expression of Caspase-3 and its activation.
CONCLUSION: Telomerase activity and Caspase-3 expression are changed in human hepatocellular carcinoma cell line SMMC-7721 treated with all-trans retinioc acid. The inhibition of telomerase activity and the activation of Caspase-3 may be the key steps through which ATRA inhibits the proliferation of SMMC-7721 cell line.
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Affiliation(s)
- Yun-Feng Piao
- Department of Gastroenterology, the First Hospital of Jilin University, Changchun, 130021, Jilin Province, China
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Shats I, Milyavsky M, Erez N, Rotter V. The murine telomerase catalytic subunit shares the PAb-240 mutant specific epitope of the p53 protein. FEBS Lett 2003; 546:321-4. [PMID: 12832061 DOI: 10.1016/s0014-5793(03)00607-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Many tumorigenic p53 mutants gain a common antigenic epitope that is recognized by the PAb-240 antibody. Database search identified the presence of this epitope in several other proteins, including several antibodies and the catalytic subunit of mouse telomerase, mTERT. These antibodies may represent a part of the previously demonstrated anti-idiotypic network built around p53. In the present study we demonstrate that the PAb-240 antibody was able to inhibit telomerase activity in extracts from both mouse and human tumor cells. The recognition of mTERT by PAb-240 is demonstrated by Western blotting and by using blocking peptides derived from mTERT. The existence of a shared epitope between mutant p53 and telomerase may suggest that the two proteins contribute to malignant transformation through a common pathway.
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Affiliation(s)
- Igor Shats
- Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
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Mikhailova MV, Winters CJ, Andreoli TE. Cl- channels in basolateral TAL membranes. XVI. MTAL and CTAL cells each contain the mRNAs encoding mmClC-Ka and mcClC-Ka. Kidney Int 2002; 61:1003-10. [PMID: 11849455 DOI: 10.1046/j.1523-1755.2002.00218.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Our prior data indicate that two separate but homologous basolateral chloride (Cl-) channels, mmClC-Ka and mcClC-Ka, are the principal mediators of net Cl- absorption in mouse medullary thick ascending limb (MTAL) and cortical thick ascending limb (CTAL) cells, respectively. In the present studies, we evaluated the possibility that there might be translational or post-translational suppression of mmClC-Ka and mcClC-Ka activity in CTAL and MTAL cells, respectively. METHODS Polymerase chain reaction (PCR) fragments were prepared that were highly specific for either mmClC-Ka or mcClC-Ka, the cDNAs encoding mmClC-Ka and mcClC-Ka, respectively. RESULTS Using reverse transcription (RT)-PCR with these highly specific products, mRNAs specific for non-homologous channel sequences in either mmClC-Ka or mcClC-Ka were present in both MTAL and CTAL cells. CONCLUSIONS Both mouse MTAL and CTAL cells contain the mRNAs encoding mmClC-Ka and mcClC-Ka. There may be translational or post-translational suppression of mmClC-Ka activity in CTAL cells, and of mcClC-Ka activity in MTAL cells.
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Affiliation(s)
- Marina V Mikhailova
- Division of Nephrology, Department of Internal Medicine, University of Arkansas College of Medicine, 4301 West Markham, Little Rock, AR 72205, USA
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Elenitoba-Johnson KS. Complex regulation of telomerase activity: implications for cancer therapy. THE AMERICAN JOURNAL OF PATHOLOGY 2001; 159:405-10. [PMID: 11485897 PMCID: PMC1850547 DOI: 10.1016/s0002-9440(10)61710-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- K S Elenitoba-Johnson
- Department of Pathology, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132, USA.
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