| Abstract |
Hepatocellular carcinoma(HCC) is one of the most common malignant tumors worldwide with a poor prognosis and an annual incidence of one million cases. The available treatments so far have not proved very efficient therefore there is a growing need for a better understanding of the biology of the disease and careful analysis of the molecular and cellular pathways involved in hepatocarcinogenesis. Angiogenesis has a critical role in the development of cancer since early neoplasias must develop angiogenic ability to facilitate their expansion to a larger size. One of the factors implicated in the process of angiogenesis in TGFβ, which also controls a wide range of cellular functions. Several studies have established the dual role of TGFβ in cancer because it can either act as a tumor suppressor via its autocrine action or as tumor enhancer, since it can induce angiogenesis and promote tumor growth. In our study we wanted to investigate the role of all three TGFβs (TGF1,2,3) and their signaling receptors (TGFβ1R,-2R,-3R) in human hepatocellular carcinoma using semi-quantitative RT-PCR analysis. Our goals were: a) to evaluate the mRNA expression profile of TGFβ1,2,3 and the receptors TGFβ type I, II and III (TGFβ1R, TGFβ2R TGFβ3R) in a total of 45 hepatocellular carcinoma samples and compare the transcript levels of the TGFβ family in the tumor samples with those in the normal samples and b)to compare mRNA expression of TGFβ1,2,3 and receptors in the hepatocellular carcinoma group, in order to find co-expression patterns in this group. Our results indicate that a part of the HCC samples do not express any of the TGFβ ligands and receptors but this was not the case in normal samples where we found significant levels of expression of all the ligands and receptors. We observed that about 31% of hepatocellular tumors express TGFβ1 and TGFβ2R but lack any detectable expression of the other two receptors, type I and type III. This co-expression of TGFβ1 and TGFβ2R was further established since Spearmans analysis revealed a positive correlation between these two members of the TGFβ family (P < 0.0001). Our findings show that the signal transduction pathway is not functional since TGFβ1 is unable to form a complex in the absence of a second receptor. Therefore we suggest that TGFβ has lost its growth inhibitory role and probably promotes tumor proliferation, by a variety of mechanisms, in the process of hepatocellular carcinogenesis.
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Ο ρόλος του μετασχηματίζοντος αυξητικού παράγοντα (TGFβ)και του σηματοδοτικού μονοπατιού στην ανάπτυξη του ηπατοκυτταρικού καρκινώματος
