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Endocrine-Related Cancer 12 (1) 135 -148     DOI: 10.1677/erc.1.00897
Copyright © 2005 by the Society for Endocrinology
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Expression profiling of androgen-dependent and -independent LNCaP cells: EGF versus androgen signalling

Josien K Oosterhoff, J Anton Grootegoed and Leen J Blok

Department of Reproduction and Development, Erasmus MC, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands

(Requests for offprints should be addressed to L J Blok; Email: l.blok{at}erasmusmc.nl)

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.




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