Cancer Research Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine  Joint Metastasis Research Society-AACR Conference on Metastasis
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[Cancer Research 57, 2661-2667, July 1, 1997]
© 1997 American Association for Cancer Research

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HSP27 as a Mediator of Confluence-dependent Resistance to Cell Death Induced by Anticancer Drugs1

Carmen Garrido2, Patrick Ottavi, Annie Fromentin, Arlette Hammann, André-Patrick Arrigo, Bruno Chauffert and Patrick Mehlen

Institut National de la Santé et de la Recherche Médicale CJF 94-08. Faculté de Medecine, 7 Boulevard Jeanne d'Arc, 21033 Dijon Cedex, France [C. G., P. O., A. F., A. H., B. C.], and Laboratoire du Stress Cellulaire, Centre National de la Recherche Scientifique UMR-5534, Université Claude Bernard Lyon-1, 69622 Villeurbanne, France [A-P. A., P. M.]

Resistance of colorectal cancer cells to chemotherapeutic drugs increases as cells reach confluence. Here we show that the small stress protein HSP27, which has been described to block necrotic and apoptotic cell death, accumulates in confluent human colorectal cancer cell lines HT-29 and Caco2. Cell confluence also induces HSP27 phosphorylation and changes in its intracellular distribution. We also show that overexpression of human HSP27 by transfection of HT-29 cells increased the resistance of cells to doxorubicin or cisplatin and prevented drug-induced apoptosis. Interestingly, nonconfluent HSP27-transfected cells and confluent control cells in which HSP27 is expressed at the same level displayed a similar drug resistance. HSP27-transfected cells did not exhibit an enhanced resistance when they reached confluence, nor was there an increased accumulation of HSP27. We have previously shown that HSP27 expression blocks tumor necrosis factor-induced cell death as a result of decreasing intracellular reactive oxygen species (ROS). Here we show that HSP27 overexpression in HT-29 cells, obtained either by transfection or by growing the cells at high density, correlated with a significant ROS decrease. We conclude that cell confluent-dependent HSP27 accumulation, probably due to its ability to decrease ROS levels, is essential for the establishment of the resistance of colorectal cancer cells when reaching confluence.

1 Supported by the Conseil Regional de la Bourgogne, the Ligue Bourguignonne contre le Cancer, Association pour la Recherche sur le Cancer Grant 6011, Institut National pour la Santé et la Recherche Medicale Grant 930.501, and the Region Rhône-Alpes.

2 To whom requests for reprints should be addressed. Phone: 33-03-80-67-1788.

Received 12/10/96. Accepted 4/30/97.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 1997 by the American Association for Cancer Research.