AIM: To study the expression of a disintegrin and metalloproteinase 17 (ADAM17) mRNA in hepatocellular carcinoma (HCC) and to evaluate the relationship between ADAM17 mRNA expression and clinicopathological features of HCC.

METHODS: Hepatocellular carcinomas (HCC) from 31 cases were divided into small HCC (SHCC), nodular HCC (NHCC) and solitary large HCC (SLHCC) according to tumor diameter and the number of nodes. ADAM17 mRNA expressions were compared among those groups by means of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The relationship between ADAM17 mRNA expression level and clinicopathological features of HCC was evaluated.

RESULTS: NHCC had lower differentiation and was more frequently of microvascular invasion (10/12) than SHCC (3/11) and SLHCC (3/8) (P < 0.05), but no statistical difference was observed between SHCC and SLHCC comparing their clinicopathological features. ADAM17 mRNA expression was detected in 77.4% (24/31) of HCC tissues and was significantly higher than that in paired non-cancerous liver tissues in which only 35.5% (11/31) of the samples were detected of the expression (P < 0.05). The expression of ADAM17 mRNA was much higher in NHCC than in SHCC and SLHCC (P < 0.05), while no significant difference was discovered between SHCC and SLHCC. The quantities of ADAM17 mRNA were significantly higher in poorly differentiated HCC than in well or moderately differentiated HCC, but no statistical difference was found concerning liver cirrhosis, tumor capsule formation or microvascular invasion of the cancer.

CONCLUSION: The increased expression of ADAM17 may play a key role in the development of HCC. The expression levels of ADAM17 mRNA varied among different pathological types of HCC. Lower mRNA expression of ADAM17 mRNA in SLHCC may be associated with the better molecular pathological features of SLHCC.

• ADAM Proteins
• ADAM17 Protein
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/physiopathology
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Liver/pathology
• Liver/physiology
• Liver Neoplasms/pathology
• Liver Neoplasms/physiopathology
• Male
• Metalloendopeptidases/genetics
• RNA, Messenger/analysis
• Transcription, Genetic

AIM: Many growth factors, such as epidermal growth factor (EGF), are associated with the carcinogenesis. EGF plays its role in the proliferation of hepatoma cells through binding with EGF receptor (EGFR) and a series of signal transduction. But the postreceptor pathway is still not clear. In the present experiment, we studied the effect of tyrosine kinase, protein kinase C, Na⁺/H⁺ exchange, calmodulin and voltage-dependent Ca²⁺ channel on EGF-induced hepatoma cell proliferation.

METHODS: Hepatoma cell line SMMC7721 was cultured in RPMI1640 serum-free medium. In order to study the effect of thyrosine kinase, protein kinase C, Na⁺/H⁺ exchange, calmodulin and voltage-dependent Ca²⁺ channel on human heptoma cell proliferation induced by epidermal growth factor (EGF), DNA synthesis rate of hepatoma cells was measured by the method of ³H-TdR incorporation.

RESULTS: EGF (10^-9 M) stimulated the proliferation of heptoma cells significantly (³H-TdR incorporation was 1880 ± 281 cpm/well, P < 0.05), and this effect was significantly inhibited by tyrosine kinase inhibitor genistein (³H-TdR incorporation was 808 ± 209 cpm/well, P < 0.001). Calmodulin inhibitor W-7, protein kinase C inhibitor H-7 and Na⁺/H⁺ exchange inhibitor amiloride individually had significant inhibiting effect on EGF-induced proliferation of hepatoma cells (³H-TdR incorporation was 978 ± 87.3 cpm/well, 1241 ± 147 cpm/well, 1380 ± 189 cpm/well, respectivly, P < 0.001, P < 0.01, P < 0.05), but they all had no effect on the basal level proliferation of cultured hepatoma cells (³H-TdR incorporation was 1284 ± 260 cpm/well, 1179 ± 150 cpm/well, 1392 ± 152 cpm/well, respectivly, ³H-TdR incorporation of the control was 1353 ± 175 cpm/well, P > 0.05). Voltage-dependent Ca²⁺ channel inhibitor verapamil had no inhibition on EGF-induced proliferation of hepatoma cells (³H-TdR incorporation was 1637 ± 133 cpm/well, P > 0.05), it also had no effect on the basal level proliferation of cultured hepatoma cells (³H-TdR incorporation was 1196 ± 12 cpm/well, P > 0.05).

CONCLUSION: Our data suggest that tyrosine kinase, Ca²⁺-calmodulin-dependent pathway, protein kinase C and Na⁺/H⁺ exchange play a critical role in EGF-induced proliferation of hepatoma cells and that the effect of EGF is independent of voltage-dependent Ca²⁺ channel.

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Division/drug effects
• Cell Division/physiology
• Enzyme Inhibitors/pharmacology
• Epidermal Growth Factor/pharmacology
• Genistein/pharmacology
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Sodium-Hydrogen Exchangers/metabolism
• Sulfonamides/pharmacology
• Tumor Cells, Cultured