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Function analysis of estrogenically regulated protein tyrosine phosphatase γ (PTPγ) in human breast cancer cell line MCF-7

Abstract

Protein tyrosine phosphatase γ (PTPγ) is a member of the receptor-like family of tyrosine phosphatases and has been implicated as a tumor suppressor gene in kidney and lung cancers. Based on our previous findings, we hypothesize that PTPγ is a potential estrogen-regulated tumor suppressor gene in human breast cancer. To examine the effects of PTPγ on growth of MCF-7 human breast cancer cells and compare the estrogenic responses of human breast cells with different PTPγ expression levels, we established several stably transfected MCF-7 cell lines expressing different levels of PTPγ, which were confirmed by RT–PCR and immunostaining. In our work, we used the antisense construct to breakdown endogenous PTPγ level in MCF-7 cells. The results from doubling time assay suggested that PTPγ is capable of inhibiting MCF-7 breast cancer cell growth. We further demonstrated that PTPγ is able to inhibit anchorage-independent growth of breast cancer cells in soft agar and reduce the estrogenic responses of MCF-7 cell proliferation to estradiol-17β (E2) and zeranol (Z, a nonsteroidal growth promoter with estrogenic activity). Our data suggest that PTPγ may function as an important modulator in regulating the process of tumorigenesis in human breast.

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References

  • Barnea G, Silvennoinen O, Shaanan B, Honegger AM, Canoll PD, D'Eustachio P, Morse B, Levy JB, LaForgia S, Huebner K, Musacchio JM, Sap J and Schlessinger J . (1993). Mol. Cell. Biol., 13, 1497–1506.

  • Gaits F, Li RY, Ragab A, Ragab-Thomas JMF and Chap H . (1995). Biochem. J., 311, 97–103.

  • Kaplan R, Morse B, Huebner K, Croce C, Ravera M, Ricca G, Jaye M and Schlessinger J . (1990). Proc. Natl. Acad. Sci. USA, 87, 7000–7004.

  • Klarlund JK . (1985). Cell, 41, 707–717.

  • Krop IE, Sgroi D, Porter DA, Lunetta KL, LeVangie R, Seth P, Kaelin CM, Rhei E, Bosenberg M, Schnitt S, Marks JR, Pagon Z, Belina D, Razumovic J and Polyak K . (2001). Proc. Natl. Acad. Sci. USA, 98, 9796–9801.

  • Krueger NX and Saito H . (1992). Proc. Natl. Acad. Sci. USA, 8, 7417–7421.

  • Krueger NX, Streuli M and Saito H . (1990). EMBO J., 9, 3241–3252.

  • Kulp SK, Liu S, Sugimoto Y, Brueggemeier RW and Lin YC . (2000). Biol. Reprod., 62 (Suppl 1), 181–182.

  • Laborda J . (1991). Nucleic Acids Res., 19, 3998.

  • LaForgia S, Lasota J, Latif F, Boghosian-sell L, Kastury K, Ohta M, Druck T, Atchison L, Cannizzaro L, Barnea G, Schlessinger J, Modi W, Kuzmin I, Tory K, Zbar B, Croce CM, Lerman M and Huebner K . (1993). Cancer Res., 53, 3118–3124.

  • LaForgia S, Morse B, Levy J, Barnea G, Cannizzaro LA, Li F, Nowell PC, Boghosian-sell L, Glick J, Weston A, Harris CC, Drabkin H, Patterson D, Crose CM, Schlessinger J and Huebner K . (1991). Proc. Natl. Acad. Sci. USA, 88, 5036–5040.

  • Levy JB, Canoll PD, Silvennoinen O, Barnea G, Morse B, Honegger AM, Huang J-T, Cannizzaro LA, Park S-H, Druck T, Huebner K, Sap J, Ehrlich M, Musacchio JM and Schlessinger J . (1993). J. Biol. Chem., 268, 10573–10581.

  • Lin YC, Chang CJG, Sugimoto Y, Chen R, Canatan H, Brueggemeier RW and Dayton MA . (1994). Proceedings of the American Association for Cancer Research 85th Annual Meeting, Vol. 35, 607a (Abstract #3619).

  • Liu S, Kulp SK, Sugimoto Y, Jiang J, Chang HL and Lin YC . (2002). Breast Cancer Res. Treat., 71, 21–35.

  • Lubinski J, Hadaczek P, Podolski J, Toloczko A, Sikorski A, McCue P, Druck T and Huebner K . (1994). Cancer Res., 54, 3710–3713.

  • Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A and Chambon P . (1982). Nucleic Acids Res., 10, 7895–7903.

  • Poliseno L, Mariani L, Collecchi P, Piras A, Zaccaro L and Rainaldi G . (2002). Cancer Chemother. Pharmacol., 50, 127–130.

  • Shock LP, Bare DJ, Klinz PF and Maness PF . (1995). Mol. Brain Res., 28, 110–116.

  • Sorio C, Melotti P, D'Arcangelo D, Mendrola J, Calabretta B, Croce CM and Huebner K . (1997). Blood, 90, 49–57.

  • Sorio C, Mendrola J, Lou Z, Laforgia S, Croce CM and Huebner K . (1995). Cancer Res., 55, 4855–4864.

  • Tsukamoto T, Takahashi T, Ueda R, Hibi K, Saito H and Takahashi T . (1992). Cancer Res., 51, 3506–3509.

  • van Niekerk CC and Poels LG . (1999). Cancer Lett., 137, 61–73.

  • Zheng J, Kulp SK, Zhang Y, Sugimoto Y, Dayton MA, Govindan MV, Brueggemeier RW and Lin YC . (2000). Anticancer Res., 20, 11–20.

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Acknowledgements

This study was supported by Department of Defense Breast Cancer Research Program Grants DAMD 8140 and 9341, and NIH Grants CA 94718 and CA 95915. MIUR 60%, Fondazione Cassa di Risparmio di Verona (Bando 2001) and Consorzio per gli Studi Universitari in Verona, Italy. We thank Dr Kay Huebner for the critical reading of this manuscript.

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Correspondence to Young C Lin.

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Liu, S., Sugimoto, Y., Sorio, C. et al. Function analysis of estrogenically regulated protein tyrosine phosphatase γ (PTPγ) in human breast cancer cell line MCF-7. Oncogene 23, 1256–1262 (2004). https://doi.org/10.1038/sj.onc.1207235

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