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

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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.

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Acknowledgements

The authors wish to express their gratitude to the Department of Science and Technology-Promotion of University Research and Scientific Excellence (DST-PURSE) [SR/59/Z-23/2010/38(c)] and University Grant Commission-Centre with Potential for Excellence in Particular Area (UGC-CPEPA) [8-2/2008(NS/PE)], New Delhi for providing financial support. The authors also wish to express their gratitude to the Department of Microbiology and Biotechnology, Bangalore University, Bengaluru for providing the DST-FIST, UGC-SAP, and department facility.

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  1. Department of Microbiology and Biotechnology, Bangalore University, Jnana Bharathi, Bengaluru, 560 056, Karnataka, India

    K. Kavya, M. Naveen Kumar, Rajeshwari H. Patil, Shubha M. Hegde, K. M. Kiran Kumar, Rashmi Nagesh & S. Chidananda Sharma

  2. Department of Bioinformatics and Biotechnology, Karnataka State Women’s University, Jnanashakthi Campus, Vijayapura, 586 108, Karnataka, India

    R. L. Babu

  3. Department of Biology and Center for Biotechnology and Biomedical Sciences, Norfolk State University, Norfolk, VA, USA

    R. L. Babu & Govindarajan T. Ramesh

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  1. K. Kavya
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  2. M. Naveen Kumar
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Kavya, K., Kumar, M.N., Patil, R.H. et al. Differential expression of AP-1 transcription factors in human prostate LNCaP and PC-3 cells: role of Fra-1 in transition to CRPC status. Mol Cell Biochem 433, 13–26 (2017). https://doi.org/10.1007/s11010-017-3012-2

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