TY - JOUR
T1 - Dysregulation of the TGF-β postreceptor signaling pathway in cell lines derived from primary or metastatic ovarian cancer
AU - Xi, Ling
AU - Hu, Wei
AU - Meng, Li
AU - Zhou, Jianfeng
AU - Lu, Yunping
AU - Wang, Changyu
AU - Ma, Ding
N1 - Funding Information:
XI Ling, female, born in 1972, M. D. , Ph. D.. Doctor in Charge " This project was supported by grants from the National Crackajack Youth Fonndation (30025017) and the National Emphasis Basis Research Project of China (2002CB513100).
PY - 2004
Y1 - 2004
N2 - 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 (TβR II), 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 TβR II 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 gene was 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 be related to a decreased expression of Smad4, which mediates TGF-β induced growth inhibition, 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.
AB - 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 (TβR II), 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 TβR II 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 gene was 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 be related to a decreased expression of Smad4, which mediates TGF-β induced growth inhibition, 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.
KW - C-myc
KW - CDC25A
KW - Ovarian cancer cells
KW - Smad4
KW - Transforming growth factor-b
KW - TβR II
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M3 - Article
C2 - 15165118
AN - SCOPUS:16544392924
SN - 0257-716X
VL - 24
SP - 62
EP - 65
JO - Journal of Huazhong University of Science and Technology - Medical Science
JF - Journal of Huazhong University of Science and Technology - Medical Science
IS - 1
ER -