Blanquart Christophe, Karouri Salah-Eddine, Issad Tarik
Institut Cochin, Université Paris Descartes, CNRS, UMR, Paris, France.
Biochem Biophys Res Commun. 2009 Oct 2;387(4):748-53. doi: 10.1016/j.bbrc.2009.07.105. Epub 2009 Jul 25.
The protein tyrosine phosphatase 1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) were initially thought to be mainly anti-oncogenic. However, overexpression of PTP1B and TC-PTP has been observed in human tumors, and recent studies have demonstrated that PTP1B contributes to the appearance of breast tumors by modulating ERK pathway. In the present work, we observed that decreasing the expression of TC-PTP or PTP1B in MCF-7 cells using siRNA reduced cell proliferation without affecting cell death. This reduction in proliferation was associated with decreased ERK phosphorylation. Moreover, selection of tamoxifen-resistant MCF-7 cells, by long-term culture in presence of 4-OH tamoxifen, resulted in cells that display overexpression of PTP1B and TC-PTP, and concomitant increase in ERK and STAT3 phosphorylation. siRNA experiments showed that PTP1B, but not TC-PTP, is necessary for resistance to 4-OH tamoxifen. Therefore, our work indicates that PTP1B could be a relevant therapeutic target for treatment of tamoxifen-resistant breast cancers.
蛋白酪氨酸磷酸酶1B（PTP1B）和T细胞蛋白酪氨酸磷酸酶（TC-PTP）最初被认为主要具有抗癌作用。然而，在人类肿瘤中已观察到PTP1B和TC-PTP的过表达，并且最近的研究表明，PTP1B通过调节ERK途径促进乳腺肿瘤的出现。在本研究中，我们观察到使用小干扰RNA（siRNA）降低MCF-7细胞中TC-PTP或PTP1B的表达可减少细胞增殖，而不影响细胞死亡。这种增殖的减少与ERK磷酸化的降低有关。此外，通过在4-羟基他莫昔芬存在下长期培养来选择对他莫昔芬耐药的MCF-7细胞，结果得到的细胞显示PTP1B和TC-PTP过表达，同时ERK和STAT3磷酸化增加。siRNA实验表明，PTP1B而非TC-PTP是对4-羟基他莫昔芬耐药所必需的。因此，我们的研究表明PTP1B可能是治疗他莫昔芬耐药乳腺癌的一个相关治疗靶点。
