Lee Moon Young, Joung Youn Hee, Lim Eun Joung, Park Jong-Hwan, Ye Sang-Kyu, Park Taekyu, Zhang Zheng, Park Dong Ki, Lee Kwang Jeon, Yang Young Mok
Laboratory of Human Genetics, Department of Pathology, College of Medicine and Bio-Food and Drug Research Center at Konkuk University, Chungju 380-701, Korea.
Breast. 2006 Apr;15(2):187-95. doi: 10.1016/j.breast.2005.05.005. Epub 2005 Aug 3.
Several constitutively activated signal transducers and activators of transcription (STAT) proteins have been observed in a wide number of human cancer cell lines and primary tumors. Normal cells maintain normoxic conditions but tumor cells are characteristically hypoxic. We studied the altered activation and tyrosine phosphorylation of STATs under hypoxic conditions (2% O2) or desferrioxamine (DFO) treatment in mouse mammary epithelial cells (HC11) and a human breast cancer cell line (MCF-7). STAT1, -3 and -5 proteins are especially important and are observed at elevated levels in tumorigenesis. We also investigated the serine phosphorylation of STAT1, -3, and -5 under hypoxic conditions or DFO treatment in HC11 and MCF-7 cells. Here we show that DFO or hypoxia stimulates the tyrosine and/or serine phosphorylation and the expression of STAT proteins in breast cancer cells. Our data suggest that DFO or hypoxic condition is a critical stimulator for the activation of STAT proteins in breast cancer cells. These results may provide the basis for identifying another mechanism of breast tumorigenesis via the JAK/STAT pathway in hypoxia. Also, activation of STAT proteins by hypoxia may play an important role in the physiological phenomenon of embryonic stem cells and old cells with hypoxic conditions.
在众多人类癌细胞系和原发性肿瘤中已观察到几种组成型激活的信号转导子和转录激活子（STAT）蛋白。正常细胞维持常氧条件，但肿瘤细胞的特征是缺氧。我们研究了在缺氧条件（2% O₂）或去铁胺（DFO）处理下，小鼠乳腺上皮细胞（HC11）和人乳腺癌细胞系（MCF-7）中STATs的激活改变和酪氨酸磷酸化情况。STAT1、-3和-5蛋白尤为重要，且在肿瘤发生过程中水平升高。我们还研究了在缺氧条件或DFO处理下，HC11和MCF-7细胞中STAT1、-3和-5的丝氨酸磷酸化情况。在此我们表明，DFO或缺氧会刺激乳腺癌细胞中STAT蛋白的酪氨酸和/或丝氨酸磷酸化以及表达。我们的数据表明，DFO或缺氧条件是乳腺癌细胞中STAT蛋白激活的关键刺激因素。这些结果可能为通过缺氧条件下的JAK/STAT途径识别乳腺癌发生的另一种机制提供依据。此外，缺氧对STAT蛋白的激活可能在胚胎干细胞和处于缺氧条件下的衰老细胞的生理现象中起重要作用。
