title: Differential expression of AP-1 transcription factors in human prostate LNCaP and PC-3 cells: role of Fra-1 in transition to CRPC status.
abstract: Androgen receptor (AR) signaling axis plays a vital role in the development of prostate and critical in the progression of prostate cancer. Androgen withdrawal initially regresses tumors but eventually develops into aggressive castration-resistant prostate cancer (CRPC). Activator Protein-1 (AP-1) transcription factors are most likely to be associated with malignant transformation in prostate cancer. Hence, to determine the implication of AR and AP-1 in promoting the transition of prostate cancer to the androgen-independent state, we used AR-positive LNCaP and AR-negative PC-3 cells as an in vitro model system. The effect of dihydrotestosterone or anti-androgen bicalutamide on the cell proliferation and viability was assessed by MTT assay. Expression studies on AR, marker genes-PSA, TMPRSS2, and different AP-1 factors were analyzed by semi-quantitative RT-PCR and expressions of AR and Fra-1 proteins were analyzed by Western blotting. Dihydrotestosterone induced the cell proliferation in LNCaP with no effect on PC-3 cells. Bicalutamide decreased the viability of both LNCaP and PC-3 cells. Dihydrotestosterone induced the expression of AR, PSA, c-Jun, and Fra-1 in LNCaP cells, and it was c-Jun and c-Fos in case of PC-3 cells, while bicalutamide decreased their expression. In addition, constitutive activation and non-regulation of Fra-1 by bicalutamide in PC-3 cells suggested that Fra-1, probably a key component, involved in transition of aggressive androgen-independent PC-3 cells with poor prognosis.
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India.
authors.forename: K
authors.initials: K
authors.lastname: Kavya
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India.
authors.forename: M Naveen
authors.initials: MN
authors.lastname: Kumar
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India.
authors.forename: Rajeshwari H
authors.initials: RH
authors.lastname: Patil
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India.
authors.forename: Shubha M
authors.initials: SM
authors.lastname: Hegde
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India.
authors.forename: K M
authors.initials: KM
authors.lastname: Kiran Kumar
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Nagesh
authors.affiliation: Department of Bioinformatics and Biotechnology, Karnataka State Women's University, Jnanashakthi Campus, Vijayapura, 586 108, Karnataka, India.|Department of Biology and Center for Biotechnology and Biomedical Sciences, Norfolk State University, Norfolk, VA, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Babu
authors.affiliation: Department of Biology and Center for Biotechnology and Biomedical Sciences, Norfolk State University, Norfolk, VA, USA.
authors.forename: Govindarajan T
authors.initials: GT
authors.lastname: Ramesh
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India. sharma@bub.ernet.in.
authors.forename: S
authors.initials: S
authors.lastname: Chidananda Sharma
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D000099169:Fos-Related Antigen 1
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1
keywords: Androgen receptor; Bicalutamide; CRPC; Dihydrotestosterone; RT-PCR; Western blot