Zelinski D P, Zantek N D, Stewart J C, Irizarry A R, Kinch M S
Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907-1246, USA.
Cancer Res. 2001 Mar 1;61(5):2301-6.
Elevated levels of protein tyrosine phosphorylation contribute to a malignant phenotype, although the tyrosine kinases that are responsible for this signaling remain largely unknown. Here we report increased levels of the EphA2 (ECK) protein tyrosine kinase in clinical specimens and cell models of breast cancer. We also show that EphA2 overexpression is sufficient to confer malignant transformation and tumorigenic potential on nontransformed (MCF-10A) mammary epithelial cells. The transforming capacity of EphA2 is related to the failure of EphA2 to interact with its cell-attached ligands. Interestingly, stimulation of EphA2 reverses the malignant growth and invasiveness of EphA2-transformed cells. Taken together, these results identify EphA2 as a powerful oncoprotein in breast cancer.
尽管导致这种信号传导的酪氨酸激酶在很大程度上仍不清楚，但蛋白质酪氨酸磷酸化水平升高会导致恶性表型。在此我们报告，在乳腺癌的临床标本和细胞模型中，EphA2（ECK）蛋白酪氨酸激酶水平升高。我们还表明，EphA2的过表达足以赋予未转化的（MCF-10A）乳腺上皮细胞恶性转化和致瘤潜力。EphA2的转化能力与其无法与其细胞附着配体相互作用有关。有趣的是，对EphA2的刺激可逆转EphA2转化细胞的恶性生长和侵袭性。综上所述，这些结果表明EphA2是乳腺癌中一种强大的癌蛋白。
