Expression profiling of androgen-dependent and -independent LNCaP cells: EGF versus androgen signalling.
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.
Oosterhoff
Josien K
JK
Department of Reproduction and Development, Erasmus MC, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Grootegoed
J Anton
JA
Blok
Leen J
LJ
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
D000728:Androgens; D014408:Biomarkers, Tumor; D004815:Epidermal Growth Factor