Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth.
Identification of the molecular changes that promote viability and metastatic behavior of prostate cancer is critical for the development of improved therapeutic interventions. Stat5a/b and Stat3 are both constitutively active in locally-confined and advanced prostate cancer, and both transcription factors have been reported to be critical for the viability of prostate cancer cells. We recently showed that Stat3 promotes metastatic behavior of human prostate cancer cells not only in vitro but also in an in vivo experimental metastases model. In this work, we compare side-by-side Stat5a/b versus Stat3 in the promotion of prostate cancer cell viability, tumor growth, and induction of metastatic colonization in vivo. Inhibition of Stat5a/b induced massive death of prostate cancer cells in culture and reduced both subcutaneous and orthotopic prostate tumor growth, whereas Stat3 had a predominant role over Stat5a/b in promoting metastases formation of prostate cancer cells in vivo in nude mice. The molecular mechanisms underlying the differential biological effects induced by these two transcription factors involve largely different sets of genes regulated by Stat5a/b versus Stat3 in human prostate cancer model systems. Of the two Stat5 homologs, Stat5b was more important for supporting growth of prostate cancer cells than Stat5a. This work provides the first mechanistic comparison of the biological effects induced by transcription factors Stat5a/b versus Stat3 in prostate cancer.
Gu
Lei
L
Department of Cancer Biology, Medical Oncology, Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Dagvadorj
Ayush
A
Lutz
Jacqueline
J
Leiby
Benjamin
B
Bonuccelli
Gloria
G
Lisanti
Michael P
MP
Addya
Sankar
S
Fortina
Paolo
P
Dasgupta
Abhijit
A
Hyslop
Terry
T
Bubendorf
Lukas
L
Nevalainen
Marja T
MT
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; C494087:Stat3 protein, mouse; C494096:Stat5b protein, mouse