| Summary: | 碩士 === 國立臺北科技大學 === 生物科技研究所 === 98 === Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The incidence rate is much higher in developing countries than in industrialized countries. More than 75% of HCC cases occur in the Southeast Asia and sub-Saharan Africa.
There are four members belong to human epidermal growth factor receptor (EGFR; HER) family : EGFR( HER1)、HER2、HER3、HER4. Overexpression of HER1 and HER2 were found in so many types cancers including HCC. They lead the cells proliferation、differention、invasion、metastasis、antiapoptosis and angiogenesis of cancer cells. Therefore, HER1 and HER2 have been widely predicted as a biomarker in clinical purpose. To our knowledge, HER3 is different from other HER family
members. It requires heterodimerization with the other HER family members to trigger the signaling transduction. Further, the signal transction cascades involve in the tumor cell proliferation, migration, invasion, anti-apoptosis, and increased angiogenesis.The high level expression of HER3 has been observed in breast, ovarian, and lung cancer. Expression of HER3 protein in HCC using immunohistochemistry was further shown to be related to cell proliferation, intrahepatic metastasis, portal invasion and carcinoma differentiation. Accordingly, we hypothesized that not only HER1 but also HER3 may play an important role in HCC. By analyzing the gene expression level of HER1 and HER3 in six HCC cell lines and twenty paraffin tissue samples, we found that the expression level of two genes were correlated with gene structures and/or gene copy number alterations. Notably, HER3 presented either the different level of copy number changes or gene structure alterations in all six cell lines. In addition, HER1 and HER3 genes were highly expressed in Tong cell line when compared to other HCC cell lines. The FISH results showed the alteration of genes structure and increased copy number of HER1 and HER3 genes in all cell lines. While the study on the clinical HCC samples revealed that the gene structural aberrations were more common than gene copy number alterations. Most of the clinical samples presented one copy of HER1 and HER3 genes. However, further evidence from larger clinical samples is needed to clarify our current findings.
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