Cervical Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Cervical Cancer, including details on symptoms, vaccine, screening, treatment, human papilloma virus (hpv), information. | ||||||||
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Effects of human papillomavirus type 16 E7 protein on the growth of cervical carcinoma cells and immuno-escape through the TGF-beta1 signaling pathway.Xu Q, Wang S, Xi L, Wu S, Chen G, Zhao Y, Wu Y, Ma D Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, Hubei 430030, P R China. OBJECTIVE: E7 is regarded as one of the main oncoproteins of high-risk human papillomaviruses (HPVs). It may affect the transforming growth factor beta 1 (TGF-beta1) signaling pathway. In this study, the relationship between HPV-16 infection and the functions of three critical factors of the TGF-beta1/Smads pathway was explored to assess the possible role of E7 in the development of cervical cancer. METHODS: The expression of E7, TGF-beta1, TbetaR-II and Smad4 was detected by immunohistochemistry in paraffin-embedded cervical samples, and by RT-PCR and Western blotting in cervical cancer cell lines. The effect of TGF-beta1 on the growth of cervical cancer cells were tested by methyl thiazolyl tetrazolium (MTT), and the effects of HPV-16 E7 protein on normal and malignant cervical cells were investigated by flow cytometry. RESULTS: During the progression from benign to malignant lesions, the expression levels of TGF-beta1 and Smad4 increased significantly in cervical carcinoma tissues. The expression of TGF-beta1 was positively correlated with E7 expression. In vitro experiments showed that TGF-beta1 could not inhibit the proliferation of several cervical carcinoma cell lines in long-term regulation, but could inhibit immunologic reactions of peripheral blood mononuclear cells (PBMCs). Blocking E7 expression could lower the expression level of TGF-beta1 and induce cells to enter apoptosis. CONCLUSIONS: Our data indicate that HPV-16 E7 protein plays an important role during the development of cervical cancer by immuno-inhibition and stimulation of tumor cell proliferation through the TGF-beta1/Smads signaling pathway. Published 28 February 2006 in Gynecol Oncol, 101(1): 132-9.
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