Signal transducer and activator of transcription 5A/B in prostate and breast cancers.
Protein kinase signaling pathways, such as Janus kinase 2-Signal transducer and activator of transcription 5A/B (JAK2-STAT5A/B), are of significant interest in the search for new therapeutic strategies in both breast and prostate cancers. In prostate cancer, the components of the JAK2-STAT5A/B signaling pathway provide molecular targets for small-molecule inhibition of survival and growth signals of the cells. At the same time, new evidence suggests that the STAT5A/B signaling pathway is involved in the transition of organ-confined prostate cancer to hormone-refractory disease. This implies that the active JAK2-STAT5A/B signaling pathway potentially provides the means for pharmacological intervention of clinical prostate cancer progression. In addition, active STAT5A/B may serve as a prognostic marker for identification of those primary prostate cancers that are likely to progress to aggressive disease. In breast cancer, the role of STAT5A/B is more complex. STAT5A/B may have a dual role in the regulation of malignant mammary epithelium. Data accumulated from mouse models of breast cancer suggest that in early stages of breast cancer STAT5A/B may promote malignant transformation and enhance growth of the tumor. This is in contrast to established breast cancer, where STAT5A/B may mediate the critical cues for maintaining the differentiation of mammary epithelium. In addition, present data suggest that activation of STAT5A/B in breast cancer predicts favorable clinical outcome. The dual nature of STAT5A/B action in breast cancer makes the therapeutic use of STAT5 A/B more complex.
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, BLSB 309, Philadelphia, Pennsylvania 19107, USA.
Shyh-Han
SH
Tan
Marja T
MT
Nevalainen
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D025521:Tumor Suppressor Proteins