Phosphorylation and activation of STAT proteins by hypoxia in breast cancer cells.
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.
Lee
Moon Young
MY
Laboratory of Human Genetics, Department of Pathology, College of Medicine and Bio-Food and Drug Research Center at Konkuk University, Chungju 380-701, Korea.
Joung
Youn Hee
YH
Lim
Eun Joung
EJ
Park
Jong-Hwan
JH
Ye
Sang-Kyu
SK
Park
Taekyu
T
Zhang
Zheng
Z
Park
Dong Ki
DK
Lee
Kwang Jeon
KJ
Yang
Young Mok
YM
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism
D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D003676:Deferoxamine