Enhancement of Etoposide- or Irradiation-Induced Apoptosis in HER-2/neu-overexpressing Cancer Cells by Simian Virus 40 T/t-common Polypeptide
| Autor: | Chou-Hua Kuo, 郭周樺 |
|---|---|
| Rok vydání: | 2005 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 93 HER-2/neu proto-oncogene belongs to epidermal growth factor receptor families. Overexpression or gene amplification of HER-2/neu has been detected frequently in many types of human cancers, including cancers of breast, ovary, lung, kidney, colon, bladder, stomach and salivary gland. Overexpression of HER-2/neu enhances metastatic potential, chemoresistance and tumor angiogenesis. Previous studies showed that inhibition of HER-2/neu gene expression leads to suppression of tumorigenicity of HER-2/neu-overexpressing cancer cells. Therefore, HER-2/neu gene represents a suitable target for cancer therapy. Our lab previously reported that T/t-common, which contains the N-terminal common domain of simian virus 40 large T and small t antigens, can specifically repress the HER-2/neu promoter and its expression in HER-2/neu-overexpressing ovarian carcinoma SK-OV-3 cells. This phenomenon may presumably contribute to T/t-common suppression of the tumorigenic potential of these cancer cells. Furthermore, we discovered that the ability of T/t-common to suppress the tumorigenic potential of HER-2/neu-overexpressing cells is through induction of apoptosis. T/t-common specifically induces apoptosis in HER-2/neu-overexpressing cells but not in HER-2/neu low-expressing or non-transformed cells. Radiotherapy and chemotherapy are most common ways to treat cancer, but the overdose of drugs usually causes severe side effects such as vomits, alopecia, leucopenia, and susceptible to bacterial infections. In addition, chemoresistances often occurred during the prolonged period of treatment. Therefore, based on previous studies in our lab, we further investigated the possibilities of combination therapy using T/t-common and chemotherapeutic agents or irradiation in treatment of HER-2/neu-overexpressing cancers. Our data indicate that T/t-common can specifically enhance cell death induced by either etoposide or irradiation in HER-2/neu-overexpressing breast cancer cells SK-OV-3 and AU565 but not in HER-2/neu low-expressing breast cancer cells MDA-MB-231 and laryngeal cancer cells HEp-2. Further, this sensitization of HER-2/neu-overexpressing cancer cells to etoposide or irradiation is through the induction of apoptosis. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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