Olsen Hanne, Hedengran Faulds Malin A, Saharinen Pipsa, Silvennoinen Olli, Haldosén Lars Arne
Department of Medical Nutrition, Karolinska Institutet, NOVUM, S-141 86, Hudddinge, Sweden.
Biochem Biophys Res Commun. 2002 Aug 9;296(1):139-44. doi: 10.1016/s0006-291x(02)00847-1.
Prolactin, the Janus kinase 2 (JAK2) and the signal transducer and activator of transcription 5 (STAT5) are important for mammary gland development and have also been implicated in development and growth of breast tumors. In the present study we have investigated the role for JAK2 in proliferation, differentiation, and apoptosis of the mammary epithelial cell line HC11 by stably overexpressing two hyperactive JAK2 mutants. Cells expressing a JAK2 mutant consisting of only the kinase domain had high amount of nuclear STAT5 protein with low DNA-binding activity, which was rapidly induced to a DNA-binding state by prolactin treatment. Cells expressing JAK2 deleted of the kinase-like domain showed increased sensitivity to prolactin treatment compared to wild type cells. Proliferation was not affected by any of the mutants whereas the ability to undergo apoptosis was decreased implicating a transforming potential of the JAK2 mutants.
催乳素、Janus激酶2（JAK2）以及信号转导和转录激活因子5（STAT5）对乳腺发育很重要，并且也与乳腺肿瘤的发生和生长有关。在本研究中，我们通过稳定过表达两种高活性JAK2突变体，研究了JAK2在乳腺上皮细胞系HC11增殖、分化和凋亡中的作用。表达仅由激酶结构域组成的JAK2突变体的细胞具有大量核STAT5蛋白，但DNA结合活性较低，催乳素处理可迅速将其诱导至DNA结合状态。与野生型细胞相比，表达缺失激酶样结构域的JAK2的细胞对催乳素处理表现出更高的敏感性。增殖不受任何一种突变体的影响，而凋亡能力下降，这暗示了JAK2突变体具有转化潜能。
