title: c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation.
abstract: Androgens and the androgen receptor (AR) are involved in the growth and progression of prostate cancer. Our previous studies suggest that the proto-oncoprotein c-Jun is an AR coactivator that stimulates AR transactivation by mediating receptor dimerization and subsequent DNA binding. To study the physiological relevance of this c-Jun activity on AR, we have generated stable LNCaP cell lines expressing different levels of c-Jun. These cell lines exhibit a direct correlation between endogenous c-Jun levels and AR transcriptional activity and expression of endogenous androgen-regulated genes. Disruption by antisense RNA of endogenous c-Jun expression in LNCaP cells strongly compromises the androgen-dependent proliferation of these cells. In contrast, expression of a c-Jun mutant, which is fully active in coactivation of AR but deficient in AP-1 transactivation, significantly enhances androgen-dependent proliferation. This finding indicates that the coactivation function of c-Jun is sufficient for regulating androgen-induced growth of LNCaP cells. c-Jun also enhances AR transactivtion in androgen-independent LNCaP cells, which closely mimic hormone-refractory prostate cancer cells in gene expression and growth behavior. Importantly, siRNA-mediated repression of endogenous c-Jun expression results in markedly reduced growth of these cells, strongly suggesting an important biological role for c-Jun in hormone-refractory prostate cancer.
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Cai
authors.forename: C J
authors.initials: CJ
authors.lastname: Fisher
authors.forename: Z
authors.initials: Z
authors.lastname: Zheng
authors.forename: J
authors.initials: J
authors.lastname: Omwancha
authors.forename: C-L
authors.initials: CL
authors.lastname: Hsieh
authors.forename: L
authors.initials: L
authors.lastname: Shemshedini
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1