Ardini E, Agresti R, Tagliabue E, Greco M, Aiello P, Yang L T, Ménard S, Sap J
Division of Experimental Oncology, Molecular Targeting Unit, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy.
Oncogene. 2000 Oct 12;19(43):4979-87. doi: 10.1038/sj.onc.1203869.
Tyrosine phosphorylation is controlled by a balance of tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Whereas the contribution of PTKs to breast tumorigenesis is the subject of intense scrutiny, the potential role of PTPs is poorly known. RPTPalpha is implicated in the activation of Src family kinases, and regulation of integrin signaling, cell adhesion, and growth factor responsiveness. To explore its potential contribution to human neoplasia, we surveyed RPTPalpha protein levels in primary human breast cancer. We found RPTPalpha levels to vary widely among tumors, with 29% of cases manifesting significant overexpression. High RPTPalpha protein levels correlated significantly with low tumor grade and positive estrogen receptor status. Expression of RPTPalpha in breast carcinoma cells led to growth inhibition, associated with increased accumulation in G0 and G1, and delayed tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans.
酪氨酸磷酸化受酪氨酸激酶（PTK）和蛋白酪氨酸磷酸酶（PTP）之间平衡的控制。虽然PTK对乳腺肿瘤发生的作用是深入研究的主题，但PTP的潜在作用却鲜为人知。RPTPα与Src家族激酶的激活、整合素信号传导、细胞粘附和生长因子反应性的调节有关。为了探究其对人类肿瘤形成的潜在作用，我们检测了原发性人类乳腺癌中RPTPα的蛋白水平。我们发现RPTPα水平在肿瘤之间差异很大，29%的病例表现出明显的过表达。高RPTPα蛋白水平与低肿瘤分级和雌激素受体阳性状态显著相关。RPTPα在乳腺癌细胞中的表达导致生长抑制，与G0和G1期积累增加相关，并延迟肿瘤生长和转移。据我们所知，这是第一项将特定的真正PTP的表达水平与人类肿瘤疾病状态相关联的研究实例。
