The mitogcn activated protein kinase (MAPK) cascade is activated in response to ligand binding to membrane bound receptors and act as intermediates in the signal transduction process. Alterations in, or manipulations of, the MAPK pathway alters growth properties of normal cells and may potentiate tumorigenesis. We hypothesized that increased expression of MAPK plays an integral role in the progression of cellular proliferation in hepatocellular carcinoma (HCC), a system in which growth regulatory processes become disturbed. The aim of these studies was to identify alterations in the MAPK cascade in both an experimental model of HCC in the rat (H4IIE) and die human HCC disease state. Tumorigenic H4HE hepatoma cells (-10') previously grown in culture were inoculated into the right hepatic lobe of male ACI rats with reproducible parenchyma] tumor growths occurring 12-14 days post inoculation. Sham laparotomies were also performed in which saline vehicle (Q.9%w/v) was inoculated into the right hepatic lobe. Membranes were prepared from right and left hepatic lobes in both tumor bearing and sham animals. Membranes were also prepared from human HCC specimens and paired, normal liver tissue from the same individual. MAPK and MAPK kinase protein levels were determined by Western blot analysis using specific antibodies. MAPK 1,2 and MAPK Kinase 1,2 expression was not significantly different between the sahne and non-saline injected lobes of sham animals. However, membranes prepared from HCC tumors demonstrated increased expression of both MAPK and MAPK Kinase when compared to both the non-tumor bearing lobe, and sham operated animals. Furthermore, analysis of human HCC and normal tissue demonstrated increased MAPK 1,2 and MAPK Kinase 1,2 protein expression in tumor samples. In summary, the MAPK pathway is upregulated in HCC in both the human disease state aod the ex. vivo animal model compared to normal, non-tumor bearing tissue. Further studies will need to be performed to elucidate the specific mechanism of this regulation and its significance to growth and progression of bepatocellular carcinoma.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology