c-met mRNA overexpression in human hepatocellular carcinoma

Abstract

This study was aimed at assessing the presence of c-met overexpression in human hepatocellular carcinoma and at determining whether this feature is associated with a definite clinical or pathological characteristic. Expression of c-met was determined by Northern-blot hybridization of a specific probe (human met proto-oncogene) in 18 tumoral and nontumoral liver samples obtained in 18 cirrhotic patients with hepatocellular carcinoma submitted to surgical treatment. Eight of the 18 hepatocellular carcinomas exhibited c-met overexpression, with an increase ranging between 2-fold and 10-fold when compared by densitometry with the surrounding liver. By contrast, in the remaining 10 cases c-met expression was almost identical to that of the surrounding nontumoral liver tissue. Overexpression of c-met was not related to either the age, sex, etiology or functional status of the underlying liver disease, or to the size of the tumor, to its differentiation degree or to the presence of pseudocapsule invasion and existence of additional neoplastic nodules. These data indicate that almost half of the human hepatocellular carcinomas exhibit c-met overexpression. Nevertheless, the biological relevance of this characteristic is not known.

Dysregulation of growth factor signaling in human hepatocellular carcinoma

“…More than 70% of IGF-II is bound to IGFBP3, the most abundant circulating binding protein for IGFs (1996), Noguchi et al (1996), Neaud et al (1997), Guirouilh et al (2000Guirouilh et al ( , 2001) MET Upregulated in 20-48% Boix et al (1994), Suzuki et al (1994), Kiss et al (1997), Ueki et al (1997), Tavian et al (2000) TGFa (Jones and Clemmons, 1995). Thus, downregulation of IGFBPs may contribute to elevated IGF bioavailability in tumor tissues.…”

“…MET is detectable in most HCCs (B70%; Table 1; Suzuki et al, 1994;Kiss et al, 1997); however, overexpression of the receptor as compared to peritumorous liver tissue is observed in a lower number of tumor samples (20-48%; Boix et al, 1994;Suzuki et al, 1994;Kiss et al, 1997;Ueki et al, 1997;Tavian et al, 2000). This induction in HCC cells may be attributed to different molecular mechanisms, such as genomic alterations (7q gains in 16.8%; Moinzadeh et al, 2005), tumor hypoxia (Pennacchietti et al, 2003) and growth factor-dependent transcriptional activation of MET (e.g.…”

“…In the majority of the studies, increased levels of MET in HCCs do not correlate with tumor size or invasive behavior (Boix et al, 1994;Okano et al, 1999); however, one study links the expression of MET with increased intrahepatic metastasis and decreased 5-year survival of patients (Ueki et al, 1997). Additionally, overexpression of MET is detected predominantly in poorly differentiated HCCs (Daveau et al, 2003).…”

Liver hepatocyte growth factor does not always correlate with hepatocellular proliferation in human liver lesions: Its specific receptorc-met does

“…16 sion of HGF and c-met protooncogene product with the Increases in c-met pp expression have been reported in percentage of cyclin A / nuclei were compared, the closhepatocytes of many benign and malignant human liver tisest relationship was between c-met protooncogene prodsues. [17][18][19] Furthermore, in experimental hepatic regeneration, uct and cyclin A. In 11 of 20 HCCs (55%), there was no the overexpression of c-met pp in OCs matches that of HGF correlation between HGF positivity and cyclin A.…”

“…1 Originally identified in the It has been shown that HCCs overexpress c-met pp in comserum of partially hepatectomized rats, 2 HGF has also been parison with normal liver. [17][18][19] We therefore decided to invesisolated from humans and its gene cloned. [3][4][5] HGF's receptor tigate the expression of HGF and c-met pp in a series of has been characterized as the product of the protooncogene benign and malignant liver lesions that involve mature pac-met, 6 which is overexpressed in solid tumors, such as colonic renchymal cells, malignant hepatocytes, and OCs.…”