The Oncogenic Role of Stat Transcription Factors in Breast Cancer
Katherine Hughes and Christine J. Watson
The STAT family of proteins is comprised of seven transcription factors that have diverse roles in tissue homeostasis, differentiation and immune function. The Jak/Stat signaling pathway is frequently dysregulated in tumors of the haematopoietic system and in solid tumors of many tissue types. The STATs most frequently found to be constitutively active in cancers, as judged by tyrosine phosphorylation, are STAT3 and STAT5. The first association of aberrant STAT activity and cancer was found in the human breast but is not restricted to humans as phospho‑STAT3 has been detected in neoplastic feline mammary gland tissue by immunohistochemistry. Several members of the STAT family are essential for normal mouse mammary gland development: Stat6 for commitment to the alveolar lineage during pregnancy, Stat5 for signaling downstream of prolactin and functional differentiation and Stat3 for inducing cell death and tissue remodeling during postlactational regression. The activity of STATs in tumors has made these molecules attractive targets for therapy.