Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft

Palma Rocchi, Xavier Muracciole, Frederic Fina, Dave J. Mulholland, Gilles Karsenty, Jacqueline Palmari, L'Haucine Ouafik, Franck Bladou, Pierre Marie Martin

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish
Pages (from-to)9111-9119
Number of pages9
Issue number56
StatePublished - 2 Dec 2004
Externally publishedYes


  • Androgen-independence
  • LuCaP 23.1 xenograft
  • Molecular expression analysis
  • Prostate cancer


Dive into the research topics of 'Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft'. Together they form a unique fingerprint.

Cite this