title: Expression profiling of androgen-dependent and -independent LNCaP cells: EGF versus androgen signalling.
abstract: 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.
authors.affiliation: Department of Reproduction and Development, Erasmus MC, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Josien K
authors.initials: JK
authors.lastname: Oosterhoff
authors.forename: J Anton
authors.initials: JA
authors.lastname: Grootegoed
authors.forename: Leen J
authors.initials: LJ
authors.lastname: Blok
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D014408:Biomarkers, Tumor; D004815:Epidermal Growth Factor