Prostate cancer development often includes a shift from androgen-dependent to androgen-independent growth. It is hypothesized that, during this transition, growth factors like the epidermal growth factor (EGF) gain importance as activators of tumour cell proliferation. To study this, androgen- and EGF-regulation of growth and gene-expression was analysed in the androgen-dependent human prostate cancer cell line LNCaP-FGC (FGC) and its androgen-independent derivative line LNCaP-LNO (LNO). It was observed that androgen-dependent FGC cells require exposure to either androgens or EGF to proliferate. This is in contrast to androgen-independent LNO cells that showed significant proliferation in medium depleted of androgens and growth factors. Gene expression data were obtained for the androgen-dependent FGC and androgen-independent LNO cells cultured in the presence or absence of androgens (synthetic R1881) or EGF for different time periods. Expression profiling showed that many cell cycle genes, including a number of androgen- and EGF-regulated genes, are constitutively activated in androgen-independent LNO cells. Furthermore, the overlap between changes in gene expression activated by androgen and EGF receptor signalling pathways was found to be very high (75%). These results partly explain why androgen-independent LNO cells can proliferate in the absence of androgenic stimulation. However, possibly other, so far unknown, signal transduction pathways that induce and maintain proliferation, have also been activated.

*Signal Transduction, Androgens/*pharmacology, Epidermal Growth Factor/*pharmacology, Gene Expression Profiling, Gene Expression Regulation, Neoplastic/*drug effects, Humans, Male, Neoplasms, Hormone-Dependent/genetics/*metabolism, Oligonucleotide Array Sequence Analysis, Prostatic Neoplasms/genetics/*metabolism, Tumor Cells, Cultured, Tumor Markers, Biological/*metabolism
dx.doi.org/10.1677/erc.1.00897, hdl.handle.net/1765/13730
Endocrine - Related Cancer
Erasmus MC: University Medical Center Rotterdam

Oosterhoff, J.K, Grootegoed, J.A, & Blok, L.J. (2005). Expression profiling of androgen-dependent and -independent LNCaP cells: EGF versus androgen signalling. Endocrine - Related Cancer, 12(1), 135–148. doi:10.1677/erc.1.00897