Differential expression of AP-1 transcription factors in human prostate LNCaP and PC-3 cells: role of Fra-1 in transition to CRPC status

• Published in: Molecular and cellular biochemistry Vol. 433; no. 1-2; pp. 13 - 26
• Main Authors: Kavya, K., Kumar, M. Naveen, Patil, Rajeshwari H., Hegde, Shubha M., Kiran Kumar, K. M., Nagesh, Rashmi, Babu, R. L., Ramesh, Govindarajan T., Chidananda Sharma, S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2017; Springer; Springer Nature B.V
• Subjects: Activator protein 1; Androgen receptors; Androgens; Biochemistry; Biomedical and Life Sciences; c-Fos protein; c-Jun protein; Cardiology; Castration; Cell growth; Cell proliferation; Cells; Dihydrotestosterone; DNA binding proteins; Fra1 protein; Gene expression; Genetic research; Genetic transformation; In vitro methods and tests; Life Sciences; Medical Biochemistry; Oncology; Polymerase chain reaction; Prostate cancer; Proteins; Regression analysis; Transcription factors; Tumors; Viability; Western blotting; Western blot; Dihydrotestosterone; Bicalutamide; CRPC; RT-PCR; Androgen receptor
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-017-3012-2

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.