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 Freiss, G. Articles by Vignon, F. Search for Related Content PubMed PubMed Citation Articles by Freiss, G. Articles by Vignon, F. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Breast Cancer

Extinction of Insulin-Like Growth Factor-I Mitogenic Signaling by Antiestrogen-Stimulated Fas-Associated Protein Tyrosine Phosphatase-1 in Human Breast Cancer Cells

INSERM Unit 148 on Hormones and Cancer 34090 Montpellier, France

Steroidal (ICI 182, 780) and nonsteroidal hydroxytamoxifen (OH-Tam) antiestrogens inhibit growth factor-mitogenic activity in MCF 7 estrogen receptor-positive human breast cancer cells. Cell inhibition is correlated with an increase in membrane protein tyrosine phosphatase (PTP) activity, and the addition of orthovanadate prevents OH-Tam inhibition. After RT-PCR cloning of PTPs expressed in MCF 7 cells with primers to their catalytic domains, we have shown, by differential screening, that the expression of two enzymes, leukocyte common antigen-related PTP (LAR) and Fas-associated PTP-1 (FAP-1), was modulated by antiestrogens. By comparative RT-PCR, in situ hybridization, and Northern blot, LAR and FAP-1 mRNAs accumulation was found to be dose- and time-dependently increased by antiestrogens. To further demonstrate that PTPs were key mediators of antiestrogen-inhibitory action on the growth factor pathway, a panel of stable FAP-1 transfectants expressing low to high levels of antisense mRNAs was established. In these clones, the level of antisense RNA expression was correlated with a reduction in basal levels and a complete inhibition of antiestrogen-stimulated values of PTP activity. When FAP-1 expression was abolished, OH-Tam was no longer able to block insulin-like growth factor I mitogenic activity even though it remained strongly antiestrogenic. However, ICI 182,780 was still inhibitory, indicating that its effect was not exclusively mediated by PTP. Our data first demonstrate that a specifically regulated phosphatase (FAP-1) is implicated in the triggering of negative proliferation signals in breast cancer cells.

This article has been cited by other articles:

				M. Dromard, G. Bompard, M. Glondu-Lassis, C. Puech, D. Chalbos, and G. Freiss The Putative Tumor Suppressor Gene PTPN13/PTPL1 Induces Apoptosis through Insulin Receptor Substrate-1 Dephosphorylation Cancer Res., July 15, 2007; 67(14): 6806 - 6813. [Abstract] [Full Text] [PDF]

				A.-M. Gaben, C. Saucier, M. Bedin, G. Redeuilh, and J. Mester Mitogenic Activity of Estrogens in Human Breast Cancer Cells Does Not Rely on Direct Induction of Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase or Phosphatidylinositol 3-Kinase Mol. Endocrinol., November 1, 2004; 18(11): 2700 - 2713. [Abstract] [Full Text] [PDF]

				Z. Wang, D. Shen, D. W. Parsons, A. Bardelli, J. Sager, S. Szabo, J. Ptak, N. Silliman, B. A. Peters, M. S. van der Heijden, et al. Mutational Analysis of the Tyrosine Phosphatome in Colorectal Cancers Science, May 21, 2004; 304(5674): 1164 - 1166. [Abstract] [Full Text] [PDF]

				G. Bompard, M. Martin, C. Roy, F. Vignon, and G. Freiss Membrane targeting of protein tyrosine phosphatase PTPL1 through its FERM domain via binding to phosphatidylinositol 4,5-biphosphate J. Cell Sci., June 15, 2003; 116(12): 2519 - 2530. [Abstract] [Full Text] [PDF]

				G. Bompard, C. Puech, C. Prebois, F. Vignon, and G. Freiss Protein-tyrosine Phosphatase PTPL1/FAP-1 Triggers Apoptosis in Human Breast Cancer Cells J. Biol. Chem., November 27, 2002; 277(49): 47861 - 47869. [Abstract] [Full Text] [PDF]

				S. Oesterreich, P. Zhang, R. L. Guler, X. Sun, E. M. Curran, W. V. Welshons, C. K. Osborne, and A. V. Lee Re-expression of Estrogen Receptor {alpha} in Estrogen Receptor {alpha}-negative MCF-7 Cells Restores both Estrogen and Insulin-like Growth Factor-mediated Signaling and Growth Cancer Res., August 1, 2001; 61(15): 5771 - 5777. [Abstract] [Full Text] [PDF]

				R. E. Favoni and A. De Cupis The Role of Polypeptide Growth Factors in Human Carcinomas: New Targets for a Novel Pharmacological Approach Pharmacol. Rev., June 1, 2000; 52(2): 179 - 206. [Abstract] [Full Text] [PDF]

				A. V. Lee, J. G. Jackson, J. L. Gooch, S. G. Hilsenbeck, E. Coronado-Heinsohn, C. K. Osborne, and D. Yee Enhancement of Insulin-Like Growth Factor Signaling in Human Breast Cancer: Estrogen Regulation of Insulin Receptor Substrate-1 Expression in Vitro and in Vivo Mol. Endocrinol., May 1, 1999; 13(5): 787 - 796. [Abstract] [Full Text]