Dysregulation of the TGF-β Postreceptor＇Signaling Pathway in Cell Lines Derived from Primary or Metastatic Ovarian Cancer

• Published in: Current medical science Vol. 24; no. 1; pp. 62 - 65
• Main Author: 奚玲 胡伟 孟力 周剑峰 卢运萍 王常玉 马丁
• Format: Journal Article
• Language: English
• Published: China Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology, Wuhan 430030%Anderson Cancer Center, Taxras,USA%Southwestern Medical Center, Taxas, USA 2004
• Subjects: Animals; cdc25 Phosphatases - metabolism; Cell Line, Tumor; DNA-Binding Proteins - metabolism; Female; Humans; Mice; Mice, Nude; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Proto-Oncogene Proteins c-myc - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Signal Transduction; Smad4 Protein; Trans-Activators - metabolism; Transforming Growth Factor beta - pharmacology; 信号通道; 卵巢肿瘤; 细胞周期; 肿瘤转移; 转化生长因子-β; ovarian cancer cells; C-myc; CDC25A Smad4; TiβR; Transforming growth factor-b
• ISSN: 1672-0733; 2096-5230; 1993-1352; 2523-899X
• DOI: 10.1007/BF02830708

Transforming growth factor-beta (TGF-β) may cause cell cycle arrest, terminal differentiation, or apoptosis in most normal epithelial cells, whereas most malignant cell lines are resistant to TGF-β. Mechanisms of resistance to TGF-β caused by modulation of cell cycle regulators and/or inactivation of components of the TGF-β signaling transduction pathway such as C-myc and Smad4 are not well understood. To investigate the potential association between loss of sensitivity to TGF-β and expression status of transforming growth factor receptor Ⅱ (TβRⅡ), Smad4, CDC25A and C-myc in 14 cell lines derived from ovarian cancer, the expression levels of these genes were detected by semi-quantitative RT-PCR. Normal ovarian surface tissues were used as controls. The expression of TβRⅡ was detectable in all of 14 cell lines. The expression of Smad4 was decreased in 10 cell lines and 9 cell lines overexpressed CDC25A, as compared to normal controls. CDC25A genewas overexpressed with 88% (8/9) in tumorigenic cell lines as determined by xenografts in nude mice, and only in 20% (1/5) of non-tumorigenic cell lines (P<0.05). C-myc was not overexpressed in any of these cell lines. The loss of sensitivity to TGF-β of cell lines derived from ovarian cancers may he related to a decreased expression of Smad4, which mediates TGF-β induced growthinhibition, and/or an overexpression of CDC25A. This overexpression of CDC25A correlates with increased tumorigenicity of ovarian cancer cell lines. The loss of sensitivity to TGF-β is not associated with a lack of TβR Ⅱ.