Expression of c-Myc, c-Fos, and c-jun in hepatocellular carcinoma

Cancer. 2001 Jan 1;91(1):106-12. doi: 10.1002/1097-0142(20010101)91:1<106::aid-cncr14>3.0.co;2-2.

Abstract

Background: Increased expression of the proto-oncogene c-myc is a common phenomenon in hepatocellular carcinoma (HCC). The proto-oncogenes c-fos and c-jun are involved in cell cycle progression and cellular proliferation.

Methods: The objective of this study was to elucidate the mechanism of hepatocarcinogenesis with regard to the expressions of c-myc, c-fos, and c-jun. One hundred fifty biopsied HCC specimens were stained immunohistochemically for the above phenotypic markers both in tumor tissue and in adjacent nontumor tissue.

Results: Although the expression of c-myc was high (74%) in tumor tissue, it was significantly less compared with the expression in nontumor tissue (100%; P = 0.0002). The expression of c-myc was inversely proportional to the grade of differentiation in tumor tissue (P = 0.0108; correlation coefficient [r] = -0.244); that is, tissue with poorer histologic differentiation had a lower level of c-myc expression. There were inverse associations between the expression of c-myc and the expression of mutated p53 (P = 0.0017; r = -0.285) as well as the expression of Ki67 (P = 0.057; r = -0.147). There was significantly high expression of c-fos in tumor tissue compared with the expression in nontumor tissue (91% vs. 0%; P < 0.0001). Both the tumor tissue and the nontumor tissue had high levels of expression of c-jun (96.53% and 100%, respectively). There was a trend toward a positive association between the expression of c-fos and the expression of c-jun in tumor tissue (P = 0.07; r = 0.162).

Conclusions: Because c-myc is a known inducer of wild type p53, decreased c-myc expression may lead to uncontrolled cell growth because of the lack of p53 expression that normally induces apoptosis. The coordinated expression of c-fos and c-jun in HCC may reflect the coordinated tumor cell cycle of progression and proliferation; however, future studies are required to elucidate this possibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biopsy
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / physiopathology
  • Cell Cycle
  • Cell Transformation, Neoplastic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, fos / genetics*
  • Genes, jun / genetics*
  • Genes, myc / genetics*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Phenotype
  • Proto-Oncogene Mas