pp60c-src activation in lung adenocarcinoma.

Nine src family members are known including c-Src, c-Yes, c-Lck, c-Fyn, c-Hck, c-Lyn, c-Blk, c-Fgr and c-Yrk. They encode proteins with molecular weights of 55-62 kilodaltons (kDa), which are either cytoplasmic or membrane-associated protein tyrosine kinases. A close correlation exists between an elevated pp60c-src tyrosine kinase activity and cell transformation. However, the level of activation of pp60c-src in non-small cell lung cancers (NSCLC) remains obscure. The aim of this study was to examine the level of activity of pp60c-src in NSCLC. pp60c-src expression and in vitro protein tyrosine kinase activity in lung cancer tissue samples were measured by western blotting and in vitro kinase assays and compared with those in the surrounding non-tumour lung tissue from the same patient. pp60c-src phosphorylation was assessed by two-dimensional tryptic phosphopeptide mapping. The kinase activity of pp60c-src was significantly activated in NSCLC, especially in adenocarcinomas. In addition, the pp60c-src kinase activity increased with the size of the adenocarcinoma. Two-dimensional tryptic phosphopeptide mapping showed dephosphorylation of pp60c-src at Tyr 530 in adenocarcinomas. The proto-oncogene product, pp60c-src, was activated in NSCLC, especially in adenocarcinomas, in part through the dephosphorylation of Tyr 530. Our results suggest that activation of pp60c-src might play an important role in the progression of lung adenocarcinomas.

Expression of p33(ING1) in hepatocellular carcinoma: relationships to tumour differentiation and cyclin E kinase activity.

BACKGROUND: Inhibitor of growth-1 (ING1) is a new candidate for the tumour suppressor gene that encodes a 33k Da protein (p33(ING1)). While reduction of p33(ING1) is an important event in some human cancers, the expression of p33(ING1) in human hepatocellular carcinoma (HCC) remains to be examined. We evaluated p33(ING1) expression in various liver diseases including HCC. METHODS: Expression of p33(ING1) was evaluated immunohistochemically not only in the normal liver (n = 5), but also in specimens of chronic hepatitis (n = 39) and HCC (n = 86). We also analysed the relationship between p33(ING1) expression and cyclin E kinase activity detected by autoradiography in 29 HCCs. RESULTS: Expression of p33(ING1) was reduced in HCC, especially in moderately and poorly differentiated HCCs, and those at advanced stages. Furthermore, expression of p33(ING1) correlated inversely with cyclin E kinase activity. CONCLUSIONS: These data suggest that reduction of p33(ING1) may contribute to the process of malignant transformation, progression and dedifferentiation of HCC via an increase of cyclin E kinase activity.