Study and Identify the Metastasis-Associated Proteins in Cervical Carcinoma (I)

Carcinoma of Cervical cancer is the second most common type of cancer in women worldwide, after breast cancer, especially in developing countries. It is estimated that 500,000 new cases will be diagnosed annually in the world. In Taiwan, 4,592 cases of newly diagnosed cervical neoplasms in 1996 were reported by the Department of Health. The role of HPV infection in the development of cervical cancer is a major player in the genetic abnormalities described thus far. The effects of HPV E6 and E7 on the cell cycle genes are critical. After a successful primary treatment, the most important issue is the early detection of recurrence since advanced recurrence is always symptomatic and is not suitable for a curative treatment. Currently available serum tumor markers are not prognostic factors to predict outcome after treatment. Besides, there still no markers to indicate early metastasis and early relapse that may helpful in determining treatment modality. Hence diagnostic and prognostic markers for carcinoma of the uterine cervix is in great demand, which may have a potential importance in both basic research to understand the tumor characteristics and in clinical management to improve the survival and life quality in patients with this common malignancy. The sensitivity of tumor cell to chemo- or radio- therapy is correlated to the steroid receptor (SR) expression in some cervical cells. However, the prognostic significance of the expression SR in adenocarcinoma of the uterine cervix has been controversial. Tumor cell invasion to basement membranes is one of the hallmarks of malignant phenotype. As other malignant tumor, metastatic spread of cancer cells is responsible for most of the morbidity and mortality associated with cervical cancer. The abundance of Nm23-H1 mRNA is markedly reduced in highly metastatic tumor cell lines. Our results indicate that estradiol (E2), acting through its receptor, activated transcription of the Nm23-H1 gene. These results suggest that E2 could suppress tumor metastasis by activating the expression of the Nm23-H1 gene. Proteomics provide powerful technology for analyzing the expression levels of thousands of proteins simultaneously both in normal and tumor tissues. With technological advances in protein separation and identification in this post-genomic era, large-scale comparative analysis of proteins present in cervical tumor tissue and in its matched normal adjacent tissue might identify novel markers for the tumor. Markers that predict the tumor sensitivity to cytotoxic therapy might be retrieved through extensive comparative analysis of tumor proteins and serum proteins among patients with tumors that showed diverse sensitivity to therapy. In this study, metastasis-associated proteins will be identified via two-dimensional gel electrophoresis (2-DE). Differentially expressed polypeptides will be evaluated by computer-assisted image analysis (PDQUEST), in-gel digestion and subsequently analyzed by matrix-assisted laser desorption/ionization mass spectrometry. Differentially expressed proteins at metastasis-positive or -negative tumor identified from the analysis will be of interest for further study. In addition, the c-DNA of the genes from the differentially expressed proteins will be cloned and characterized. Their role of the metastasis-associated protein at cervix carcinoma will be studied.

Project ID:PC9308-2401
External Project ID:NSC93-2745-B182-003-URD