Molecular analysis integrating different pathways associated with androgen-independent progression in lucap 23. 1 xenograft

ABSTRACT 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 mm3) and 63 slow growing (SG) tumours (229.6±18.4 mm3), 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 5_α_-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. This work

permitted to define distinct molecular profiles related to different AI growth in the LuCaP 23.1 xenograft. Access through your institution Buy or subscribe This is a preview of subscription

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ABBREVIATIONS * AI: androgen independent * AM: adrenomedullin * FG: fast growing * FG-P: fast growing/progressing * 5_α_-R2: 5 alpha-reductase 2 * PAM: peptidyl _α_-amidating monooxygenase *

PrCa: prostate cancer * SG: slow growing * SG-P: slow growing/progressing * SG-R: slow growing/responding * TK: thymidine kinase * TS: thymidilate synthetase * uPA: urokinase plasminogen

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L and Carey M . (2003). _Cancer Res._, 63, 4552–4560. * Zudaire E, Martinez A and Cuttitta F . (2003). _Regul. Peptides_, 112, 175–183. Download references ACKNOWLEDGEMENTS We thank Dr

Robert Vessella's Laboratory, Department of Urology, University of Washington, Seattle for providing with LuCaP 23.1 xenograft. We thank Dr Lisa Valettes, Inserm U419, Nantes, who very

kindly carried out Bcl-2 TaqMan analyses. AUTHOR INFORMATION Author notes * Palma Rocchi and Xavier Muracciole: These authors contributed equally to this work AUTHORS AND AFFILIATIONS *

Laboratoire de Cancérologie Expérimentale EMI 0359/Laboratoire de Transfert d'Oncologie Biologique, Assistance Publique-Hôpitaux de Marseille (AP-HM), IFR Jean Roche, Faculté de

Médecine de Marseille, France Palma Rocchi, Frederic Fina, Jacqueline Palmari, L'Haucine Ouafik & Pierre-Marie Martin * Service de Radiothérapie, CHU Timone, AP-HM, France Xavier

Muracciole * The Prostate Centre, Jack Bell Research Centre, Vancouver, Canada Palma Rocchi & Dave J Mulholland * Service d'Urologie de l'Hôpital Salvator, AP-HM, France Gilles

Karsenty & Franck Bladou Authors * Palma Rocchi View author publications You can also search for this author inPubMed Google Scholar * Xavier Muracciole View author publications You can

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publications You can also search for this author inPubMed Google Scholar * Gilles Karsenty View author publications You can also search for this author inPubMed Google Scholar * Jacqueline

Palmari View author publications You can also search for this author inPubMed Google Scholar * L'Haucine Ouafik View author publications You can also search for this author inPubMed 

Google Scholar * Franck Bladou View author publications You can also search for this author inPubMed Google Scholar * Pierre-Marie Martin View author publications You can also search for

this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Palma Rocchi. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Rocchi, P.,

Muracciole, X., Fina, F. _et al._ Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft. _Oncogene_ 23, 9111–9119 (2004).

https://doi.org/10.1038/sj.onc.1208154 Download citation * Received: 29 January 2004 * Revised: 13 August 2004 * Accepted: 31 August 2004 * Published: 18 October 2004 * Issue Date: 02

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shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * prostate cancer *

androgen-independence * molecular expression analysis * LuCaP 23.1 xenograft