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In prostate cancer C/EBPα promotes cell growth by the loss of interactions with CDK2, CDK4, and E2F and by activation of AKT
Author(s) -
Yin Hong,
Lowery Mary,
Glass Jonathan
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20947
Subject(s) - protein kinase b , prostate cancer , cancer research , cyclin dependent kinase , cell growth , prostate , cyclin dependent kinase 2 , biology , retinoblastoma protein , cell cycle , chemistry , medicine , cancer , microbiology and biotechnology , signal transduction , biochemistry
BACKGROUND The CCAAT/Enhancer binding protein alpha (C/EBPα) is an important transcription factor for granulopoiesis and adipogenesis. While decreased expression and mutation of C/EBPα has been found in several types of tumors, the role of C/EBPα in prostate cancer has not been well characterized. METHODS We quantitatively analyzed the immunochemical staining of prostate cancer tissue and examined the growth properties of prostate cancer cells stably expressing C/EBPα by measure growth curve, cell cycle, and anchorage independent colony formation, investigated the association of C/EBPα with E2Fs and CDKs by co‐immunoprecipitation and examined the expression of CDKs and activation of AKT by Western blot analysis. RESULTS The ratio of C/EBPα expression between cancer cells close to the pseudolumen of glands and those nearer the basal cell layer was more than threefold greater than that seen in the normal prostate epithelium. Further, this ratio increased with increased Gleason score of the prostate cancer. Forced expression of C/EBPα in prostate cancer cell lines accelerated cell growth, stimulated cells into the S and G2 phases of cell cycle, and enhanced anchorage‐independent colony formation. Simultaneously, forced expression of C/EBPα increased expression of CDK2/CDK4 and nuclear PP2A, and activated AKT. In addition, C/EBPα was no longer found associated with E2F1/E2F4 and CDK2/CDK4. AKT and PPA2 inhibitors restored both the anti‐proliferation function of C/EBPα and the interaction between C/EBPα and E2F1/E2F4. CONCLUSION In prostate cancer cells C/EBPα cannot function as a tumor suppressor. Prostate 69: 1001–1016, 2009. © 2009 Wiley‐Liss, Inc.