Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of human breast cancers

Authors

  • Ion Cotarla,

    1. Department of Oncology, Georgetown University, Washington, DC, USA
    2. Graduate Program in Tumor Biology, Georgetown University, Washington, DC, USA
    Search for more papers by this author
    • The first two authors contributed equally to this paper.

  • Shuxun Ren,

    1. Department of Oncology, Georgetown University, Washington, DC, USA
    Current affiliation:
    1. Department of Anesthesiology, University of California at Los Angeles, Los Angeles, CA
    Search for more papers by this author
    • The first two authors contributed equally to this paper.

  • Ying Zhang,

    1. Biostatistics Shared Resource, Lombardi Cancer Center, Washington, DC
    Search for more papers by this author
  • Edmund Gehan,

    1. Biostatistics Shared Resource, Lombardi Cancer Center, Washington, DC
    Search for more papers by this author
  • Baljit Singh,

    1. Department of Pathology, Georgetown University, Washington, DC, USA
    Search for more papers by this author
  • Priscilla A. Furth

    Corresponding author
    1. Department of Oncology, Georgetown University, Washington, DC, USA
    2. Graduate Program in Tumor Biology, Georgetown University, Washington, DC, USA
    • Lombardi Cancer Center, Georgetown University, New Research Building, Room E518, 3970 Reservoir Rd. NW, Washington, DC 20057-1469
    Search for more papers by this author
    • Fax: +1-202-6877505


Abstract

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.

Ancillary