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Prostate. 2006 Jan 1;66(1):70-81.

E2F1 expression in LNCaP prostate cancer cells deregulates androgen dependent growth, suppresses differentiation, and enhances apoptosis.

Author information

1
Veterans Affairs Northern California Health Care System, Mather, and Department of Medical Microbiology and Immunology, University of California, Davis, USA.

Abstract

INTRODUCTION AND OBJECTIVES:

To investigate the role of E2F/RB in androgen independent proliferation, differentiation, and sensitivity to apoptotic stimuli of LNCaP prostate cancer cells.

METHODS:

The effects of E2F1 overexpression on androgen independent proliferation, differentiation, and apoptotic responses was assessed by flow cytometry, Western blot analysis and staining of nuclei.

RESULTS:

Overexpression of E2F1 in LNCaP cells confers resistance to an androgen withdrawal-mediated growth arrest, prevents differentiation, and modifies apoptotic responses. Androgen independent proliferation is associated with a dose dependent elevation of cyclin E. Cells expressing high levels of E2F1 continue to express androgen receptor and have a diminished expression of neuronal specific enolase when cultured in androgen-depleted media. Additionally, E2F1-expressing cells are more sensitive to etoposide-induced apoptosis. Western blot analysis revealed that LNCaP-E2F1 cells have elevated expression of p73, Apaf-1, caspase-3, caspase-7, but expression of caspase-8 and -9, p14(ARF), and Mcl-1, is unaltered.

CONCLUSION:

This is the first study that describes E2F1-dependent modifications of androgen dependence, differentiation, and sensitivity to apoptotic stimuli in LNCaP cells. Our analysis also identifies a subset of E2F1 targets that are instrumental in altering proliferative, differentiation, and apoptotic properties. Deregulation of the E2F/RB pathway and subsequent modification of key regulatory proteins may promote the development of hormone-refractory prostate tumors.

PMID:
16114066
DOI:
10.1002/pros.20314
[Indexed for MEDLINE]

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