title: Phosphorylation and activation of STAT proteins by hypoxia in breast cancer cells.
abstract: 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.
authors.affiliation: Laboratory of Human Genetics, Department of Pathology, College of Medicine and Bio-Food and Drug Research Center at Konkuk University, Chungju 380-701, Korea.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Joung
authors.forename: Eun Joung
authors.initials: EJ
authors.lastname: Lim
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.forename: Taekyu
authors.initials: T
authors.lastname: Park
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Park
authors.forename: Kwang Jeon
authors.initials: KJ
authors.lastname: Lee
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
mesh_terms: 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
chemical_list: 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