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The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells

Oncogene volume 21, pages 7861–7871 (2002)Cite this article

Abstract

In order to identify gene products associated with the development of acquired therapeutic resistance by prostate cancer cells, we created two novel apoptosis-resistant prostate cancer cell lines, LNCaP-TR (phorbol-ester [TPA]-Resistant) and LNCaP-SSR (Serum Starvation-Resistant) by repeated transient exposure of cultured human LNCaP cells to apoptotic stimuli followed by expansion of surviving cell populations. These cell lines were found to be cross-resistant to the alternative selective agent and also hormone-resistant when xenografted into castrated male immunodeficient mice. RNA from the LNCaP-TR line was comparatively screened using a subtractive hybridization-PCR procedure. This allowed us to identify a 249 bp cDNA fragment that hybridized to a 4.8 kb mRNA preferentially expressed by the apoptosis-resistant cells. Using RACE procedures, we cloned and sequenced the complete 4.8 kb cDNA. It is an unusual member of the protocadherin gene family containing two large overlapping open reading frames encoding homologous polypeptides, one having a signal sequence and the other lacking a signal sequence and we refer to it as protocadherin-PC. LNCaP cells directly transformed with protocadherin-PC cDNA were comparatively resistant to phorbol-ester induced apoptosis. Antibody recognition studies demonstrating the cytoplasmic nature of the protcadherin-PC translation product and its propensity to bind β-catenin suggest that it might influence the apoptotic sensitivity of prostate cancer cells through a unique mechanism.

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Acknowledgements

This work was supported by funding from US Department of Defense (DAMD-PC970137 and PC001565) and The TJ Martell Foundation for AIDS and Cancer Research, NY (to R Buttyan) and by l'Association de Recherche Contre le Cancer (ARC), le Comite des Hauts de Seine de la ligue centre le Cancer (to DK Chopin). Alexandre de la Taille was supported by a Fellowship from the French Urological Association–ARTP (France) and Francis Vacherot by a generous grant from Debat-Fournier, Inc. (France).

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  1. Min-Wei Chen, Francis Vacherot and Alexandre de la Taille: These authors contributed equally to the outcome of this project.

Authors and Affiliations

  1. The Department of Urology, The College of Physicians and Surgeons of Columbia University, New York, 10032, NY, USA

    Min-Wei Chen, Alexandre de la Taille, Ruoqian Shen, Martin Burchardt & Ralph Buttyan

  2. Department of Pathology, The College of Physicians and Surgeons of Columbia University, New York, 10032, NY, USA

    Ralph Buttyan

  3. The Computer and Informatics Resource Center of The Herbert Irving Comprehensive Cancer Center, The College of Physicians and Surgeons of Columbia University, New York, 10032, NY, USA

    Richard A Friedman

  4. Service d'Urologie, Centre Hospitalo Universitaire Henri Mondor, Assistance Publique Hopitaux de Paris, EMI INSERM 99-09, Universite Paris XII, France

    Francis Vacherot, Sixtina Gil-Diez-de-Medina & Dominique K Chopin

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Correspondence to Ralph Buttyan.

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Chen, MW., Vacherot, F., de la Taille, A. et al. The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells. Oncogene 21, 7861–7871 (2002). https://doi.org/10.1038/sj.onc.1205991

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