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Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of human breast cancers
Author(s) -
Cotarla Ion,
Ren Shuxun,
Zhang Ying,
Gehan Edmund,
Singh Baljit,
Furth Priscilla A.
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11619
Subject(s) - nuclear localization sequence , immunohistochemistry , phosphorylation , cancer research , cell nucleus , breast cancer , tyrosine , biology , tyrosine phosphorylation , lymph node , nuclear transport , mammary gland , transcription factor , cancer , pathology , cytoplasm , medicine , immunology , gene , microbiology and biotechnology , genetics , biochemistry
Signal transducers and activators of transcription (STATs) are latent cytoplasmic transcription factors that are activated and translocated into the nucleus after phosphorylation at a conserved tyrosine residue. Mouse model studies have demonstrated that activated Stat5a acts as a critical survival factor for normal, preneoplastic and malignant mammary epithelial cells. Very limited information is available, however, on the expression, tyrosine phosphorylation status and nuclear localization of Stat5a in human breast cancers. In our study, the pattern of Stat5a cellular localization was analyzed by immunohistochemistry in a series of 83 randomly selected primary human breast adenocarcinomas. Immunoprecipitation/Western blotting and immunohistochemistry assays employing different phospho‐specific antibodies verified Stat5a tyrosine phosphorylation status. Stat5a was nuclear localized and tyrosine phosphorylated in 59 of 78 (76%) breast cancers examined; 38 of 78 (49%) demonstrated Stat5a nuclear localization in more than 25% of the breast cancer cells within the adenocarcinomas. Nuclear localized Stat5a was associated positively with increased levels of histologic differentiation ( p = 0.03). A statistically significant positive association with p27 nuclear localization also was identified ( p = 0.05). No relationship was found between nuclear localized Stat5a and menopausal status, tumor size, ploidy, percentage of cells in S‐phase, lymph node metastases, ER, ErbB2, nuclear localized p21 or nuclear localized Stat5b/Stat3. As its role in human breast cancer progression and response to therapy is defined, Stat5a could become a new molecular target for breast cancer therapy. © 2003 Wiley‐Liss, Inc.