Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
Biochem Biophys Res Commun. 2010 Jan 29;392(1):83-8. doi: 10.1016/j.bbrc.2009.12.176. Epub 2010 Jan 7.
The protein tyrosine phosphatase-1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) have been implicated in down-regulation of tyrosine kinase receptors, conferring anti-oncogenic functions to these PTPases. However, recent work has shown that PTP1B is positively implicated in oncogenic properties of breast cancer cells by regulating the ERK pathway. Here, we studied the function of PTP1B and TC-PTP in IGF-2-induced growth, survival and migration of MCF-7 breast cancer cells. Using siRNA, we showed that reduction in the expression of these PTPases decreased cell growth and ERK phosphorylation. Reduction in the expression of these PTPases did not impair IGF-2 effects on cell survival to acute treatment with 4-OH Tamoxifen. In contrast, IGF-2-induced MCF-7 cell migration was markedly impaired by reduction of PTP1B or TC-PTP expression, independently of the ERK pathway. This novel finding reinforces the potential role of these PTPases as therapeutic targets for treatment of breast cancer.
蛋白酪氨酸磷酸酶-1B（PTP1B）和 T 细胞蛋白酪氨酸磷酸酶（TC-PTP）已被牵连下调酪氨酸激酶受体，为这些 PTP 酶赋予抗癌功能。然而，最近的工作表明，PTP1B 通过调节 ERK 通路，正向牵连乳腺癌细胞的致癌特性。在这里，我们研究了 PTP1B 和 TC-PTP 在 IGF-2 诱导的 MCF-7 乳腺癌细胞生长、存活和迁移中的作用。使用 siRNA，我们表明这些 PTP 酶表达的减少降低了细胞生长和 ERK 磷酸化。这些 PTP 酶表达的减少并不影响 IGF-2 对急性 4-OH 他莫昔芬处理的细胞存活的影响。相比之下，IGF-2 诱导的 MCF-7 细胞迁移明显受损，与 ERK 通路无关。这一新发现强化了这些 PTP 酶作为治疗乳腺癌的治疗靶点的潜在作用。
