Faculty Collaboration Database

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. Am J Pathol 2010 Apr;176(4):1959-72

Date

02/20/2010

Pubmed ID

20167868

Pubmed Central ID

PMC2843484

DOI

10.2353/ajpath.2010.090653

Scopus ID

2-s2.0-77950574195 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

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.

Author List

Gu L, Dagvadorj A, Lutz J, Leiby B, Bonuccelli G, Lisanti MP, Addya S, Fortina P, Dasgupta A, Hyslop T, Bubendorf L, Nevalainen MT

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Cell Survival
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Neoplasm Metastasis
Neoplasm Transplantation
Prostatic Neoplasms
STAT3 Transcription Factor
STAT5 Transcription Factor