TY - JOUR
T1 - Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft
AU - Rocchi, Palma
AU - Muracciole, Xavier
AU - Fina, Frederic
AU - Mulholland, Dave J.
AU - Karsenty, Gilles
AU - Palmari, Jacqueline
AU - Ouafik, L'Haucine
AU - Bladou, Franck
AU - Martin, Pierre Marie
PY - 2004/12/2
Y1 - 2004/12/2
N2 - After therapeutic hormone deprivation, most prostate cancer (PrCa) cells develop androgen-independent (AI) growth. PrCa is highly heterogeneous and multifocal, suggesting that several molecular processes or pathways may be contributing to AI. The human LuCaP 23.1 xenograft model retains clinical hallmarks of PrCa, including heterogeneous growth, PSA production, androgen-responsiveness and progression to AI. In this work, we studied the effect of androgen depletion (castration) on the growth of LuCaP 23.1 xenografts. A total of 100 nude mice were implanted and analysed for their growth profiles before and after castration. By 11 and 15 weeks, tumours were harvested and assessed for molecular marker expression specific for PrCa. Prior to castration we found 37 fast growing (FG) tumours (948.9 ± 76.9 mm 3) and 63 slow growing (SG) tumours (229.6 ± 18.4 mm 3), a previously undescribed result for this PrCa model. Quantitative RT-PCR showed that in comparison to SGs, FGs contained high HER1, uPA and thymidilate synthetase (TS) expression with low levels of 5a-reductase 2 mRNA. All FG tumours progressed rapidly to AI growth 5 weeks after castration (FG-P). In SG castrated tumours, 66% of tumours (SG-P) showed retarded progression (by 12 weeks) to AI, whereas 34% responded to castration (SG-R). Molecular analysis permitted us to define distinct molecular profiles integrating different pathways associated with AI progression. FG-P, and a subgroup of SG-P tumours, presented significantly high levels of peptidylglycine α-amidating monooxygenase (PAM), HER1, HER2, TS, and uPA mRNA, all of which correlated with AR expression. The second subgroup of SG-P tumours showed overexpression of the antiapoptotic gene Bcl-2. A third subgroup of SG-P tumours showed significant expression of hypoxia-related gene (adrenomedullin) after castration. TMs work permitted to define distinct molecular profiles related to different AI growth in the LuCaP 23.1 xenograft.
AB - After therapeutic hormone deprivation, most prostate cancer (PrCa) cells develop androgen-independent (AI) growth. PrCa is highly heterogeneous and multifocal, suggesting that several molecular processes or pathways may be contributing to AI. The human LuCaP 23.1 xenograft model retains clinical hallmarks of PrCa, including heterogeneous growth, PSA production, androgen-responsiveness and progression to AI. In this work, we studied the effect of androgen depletion (castration) on the growth of LuCaP 23.1 xenografts. A total of 100 nude mice were implanted and analysed for their growth profiles before and after castration. By 11 and 15 weeks, tumours were harvested and assessed for molecular marker expression specific for PrCa. Prior to castration we found 37 fast growing (FG) tumours (948.9 ± 76.9 mm 3) and 63 slow growing (SG) tumours (229.6 ± 18.4 mm 3), a previously undescribed result for this PrCa model. Quantitative RT-PCR showed that in comparison to SGs, FGs contained high HER1, uPA and thymidilate synthetase (TS) expression with low levels of 5a-reductase 2 mRNA. All FG tumours progressed rapidly to AI growth 5 weeks after castration (FG-P). In SG castrated tumours, 66% of tumours (SG-P) showed retarded progression (by 12 weeks) to AI, whereas 34% responded to castration (SG-R). Molecular analysis permitted us to define distinct molecular profiles integrating different pathways associated with AI progression. FG-P, and a subgroup of SG-P tumours, presented significantly high levels of peptidylglycine α-amidating monooxygenase (PAM), HER1, HER2, TS, and uPA mRNA, all of which correlated with AR expression. The second subgroup of SG-P tumours showed overexpression of the antiapoptotic gene Bcl-2. A third subgroup of SG-P tumours showed significant expression of hypoxia-related gene (adrenomedullin) after castration. TMs work permitted to define distinct molecular profiles related to different AI growth in the LuCaP 23.1 xenograft.
KW - Androgen-independence
KW - LuCaP 23.1 xenograft
KW - Molecular expression analysis
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=10944221722&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208154
DO - 10.1038/sj.onc.1208154
M3 - Article
C2 - 15489889
AN - SCOPUS:10944221722
SN - 0950-9232
VL - 23
SP - 9111
EP - 9119
JO - Oncogene
JF - Oncogene
IS - 56
ER -