This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dunfield, L. D. Articles by Nachtigal, M. W. Search for Related Content PubMed PubMed Citation Articles by Dunfield, L. D. Articles by Nachtigal, M. W.

TGFß-Induced Smad Signaling Remains Intact in Primary Human Ovarian Cancer Cells

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7

Address all correspondence and requests for reprints to: Mark W. Nachtigal, Dalhousie University, Department of Pharmacology, Tupper Medical Building, Halifax, Nova Scotia, Canada B3H 4H7. E-mail: . mnachtig{at}is.dal.ca

Disruptions in TGFß signaling have been implicated in various human cancers, including ovarian cancer. Our goal was to determine whether ovarian cancer cells isolated from patient ascites fluid were growth inhibited by TGFß1 treatment and further characterize the expression and activity profile of TGFß/Smad signaling components in human ovarian cancer cells. We found that 9 of 10 primary cultures of ovarian cancer cells (OC2–10) were growth inhibited by 16 pM TGFß1. One primary ovarian cancer sample (OC1) and the established ovarian cancer cell lines CaOV3 and SkOV3 continued to grow in the presence of TGFß1. All cells expressed components of the TGFß/Smad signaling pathway including TGFß1, TßRI, TßRII, Smad2, -3, -4, and Smad anchor for receptor activation. Although OC1, CaOV3, and SkOV3 are not growth inhibited by TGFß1, they can transmit the TGFß1 signal to turn on a transfected TGFß/Smad reporter gene, p3TP.lux. In addition, all cells up-regulate the endogenous TGFß target genes Smad7 and PAI-1. p15^Ink4B mRNA is also up-regulated with TGFß1 treatment in OC2–9, whereas the p15^Ink4B gene has been deleted in OC1, CaOV3, and SkOV3 cells. Homozygous deletion of p15^Ink4B may account for TGFß resistance in some populations of ovarian cancer cells. Our data demonstrate that the TGFß/Smad signaling pathway remains functional in human ovarian cancer cells and suggest that if abnormalities exist in the cellular response of TGFß signals, they must lie downstream of the Smad proteins.

This article has been cited by other articles:

				J. S. Sunde, H. Donninger, K. Wu, M. E. Johnson, R. G. Pestell, G. S. Rose, S. C. Mok, J. Brady, T. Bonome, and M. J. Birrer Expression Profiling Identifies Altered Expression of Genes That Contribute to the Inhibition of Transforming Growth Factor-{beta} Signaling in Ovarian Cancer. Cancer Res., September 1, 2006; 66(17): 8404 - 8412. [Abstract] [Full Text] [PDF]

				G. Xu, H. Zhou, Q. Wang, N. Auersperg, and C. Peng Activin Receptor-Like Kinase 7 Induces Apoptosis through Up-Regulation of Bax and Down-Regulation of Xiap in Normal and Malignant Ovarian Epithelial Cell Lines Mol. Cancer Res., April 1, 2006; 4(4): 235 - 246. [Abstract] [Full Text] [PDF]

				J. N. Kloth, G. J. Fleuren, J. Oosting, R. X. de Menezes, P. H.C. Eilers, G. G. Kenter, and A. Gorter Substantial changes in gene expression of Wnt, MAPK and TNF{alpha} pathways induced by TGF-{beta}1 in cervical cancer cell lines Carcinogenesis, September 1, 2005; 26(9): 1493 - 1502. [Abstract] [Full Text] [PDF]

				J.-S. Kim, S. J. Baek, T. Sali, and T. E. Eling The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15 Mol. Cancer Ther., March 1, 2005; 4(3): 487 - 493. [Abstract] [Full Text] [PDF]

				G. D'Andrilli, C. Kumar, G. Scambia, and A. Giordano Cell Cycle Genes in Ovarian Cancer: Steps Toward Earlier Diagnosis and Novel Therapies Clin. Cancer Res., December 15, 2004; 10(24): 8132 - 8141. [Abstract] [Full Text] [PDF]

				G. Xu, Y. Zhong, S. Munir, B. B. Yang, B. K. Tsang, and C. Peng Nodal Induces Apoptosis and Inhibits Proliferation in Human Epithelial Ovarian Cancer Cells via Activin Receptor-Like Kinase 7 J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5523 - 5534. [Abstract] [Full Text] [PDF]

				T. G. Shepherd and M. W. Nachtigal Identification of a Putative Autocrine Bone Morphogenetic Protein-Signaling Pathway in Human Ovarian Surface Epithelium and Ovarian Cancer Cells Endocrinology, August 1, 2003; 144(8): 3306 - 3314. [Abstract] [Full Text] [PDF]

				Y. Fu, E. J. Campbell, T. G. Shepherd, and M. W. Nachtigal Epigenetic Regulation of Proprotein Convertase PACE4 Gene Expression in Human Ovarian Cancer Cells Mol. Cancer Res., June 1, 2003; 1(8): 569 - 576. [Abstract] [Full Text] [PDF]