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©2005 Baishideng Publishing Group Inc. All rights reserved.
Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa
Antti J. Kivela, Seppo Parkkila, Juha Saarnio, Tuomo J. Karttunen, Jyrki Kivela, Anna-Kaisa Parkkila, Maria Bartosova, Vojtech Mucha, Michal Novak, Abdul Waheed, William S. Sly, Hannu Rajaniemi, Silvia Pastorekova, Jaromir Pastorek
Antti J. Kivela, Hannu Rajaniemi, Department of Anatomy and Cell Biology, University of Oulu, Finland
Seppo Parkkila, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Finland
Juha Saarnio, Department of Surgery, University of Oulu, Finland
Tuomo J. Karttunen, Department of Pathology, University of Oulu, Finland
Jyrki Kivela, Institute of Dentistry, University of Helsinki and Central Military Hospital, Finland
Anna-Kaisa Parkkila, Department of Neurology, Tampere University Hospital, Finland
Maria Bartosova, Vojtech Mucha, Silvia Pastorekova, Jaromir Pastorek, Center of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic
Michal Novak, Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic
Abdul Waheed, William S. Sly, Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Missouri
Author contributions: All authors contributed equally to the work.
Supported by the Grants From Sigrid Juselius Foundation, from Finnish Cultural Foundation and Finnish Dental Society, from the National Institutes of Health (DK40163, GM34182, and GM53405),from Slovak Grant Agency (2/2025), from the Slovak Government (Cancer Genomics SP 51/0280800), and from Bayer Corporation
Correspondence to: Jaromir Pastorek, Center of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic.
virupast@savba.sk
Telephone: +421-2-5930-2401 Fax: +421-2-5477-4284
Received: September 22, 2004
Revised: September 23, 2004
Accepted: November 23, 2004
Published online: May 7, 2005
AIM: To analyze possible relationships between CA IX/CA XII and pVHL expression in normal and neoplastic colorectal mucosa.
METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL control.
RESULTS: Tumor tissues were associated with a borderline increase of CA IX staining signal and slight but significant decrease of CA XII immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA XII proteins as well as between VEGF and CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12 showed a significant inverse relationship.
CONCLUSION: Our results indicate that CA9 and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels.
