title: Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of breast cancer.
abstract: The transcription factors STAT3 and STAT5 play important roles in the regulation of mammary gland function during pregnancy, lactation, and involution. Given that STAT3 and STAT5 regulate genes involved in proliferation and survival, it is not surprising that inappropriate activation of STAT3 and STAT5 occurs commonly in breast cancer. Although these proteins are structurally similar, they have divergent and opposing effects on gene expression and cellular phenotype. Notably, when STAT5 and STAT3 are activated simultaneously, STAT5 has a dominant effect, and leads to decreased proliferation and increased sensitivity to cell death. Similarly, in breast cancer, activation of both STAT5 and STAT3 is associated with longer patient survival than activation of STAT3 alone. Pharmacological inhibitors of STAT3 and STAT5 are being developed for cancer therapy, though understanding the activation state and functional interaction of STAT3 and STAT5 in a patient's tumor may be critical for the optimal use of this strategy.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Walker
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Xiang
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA. Electronic address: david_frank@dfci.harvard.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Frank
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000209:etiology*; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor
keywords: Gene expression; Oncology; Signal transduction; Transcription factors