Regular Article

British Journal of Cancer (2000) 83, 83–88. doi:10.1054/bjoc.2000.1311 www.bjcancer.com
Published online 6 June 2000

Modulation of paclitaxel resistance by annexin IV in human cancer cell lines

E Kyu-Ho Han1,2, S K Tahir1,2, S P Cherian1, N Collins1 and S-C Ng1

1Pharmaceutical Products Division, Cancer Research, Department 4N6, Building AP9, Abbott Laboratories, Abbott Park, IL 60064-3500, USA

2Authors contributed equally to this work

Received 15 November 1999; Revised 25 January 2000; Accepted 27 January 2000.

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Abstract

A recurring problem with cancer therapies is the development of drug resistance. While investigating the protein profile of cells resistant to a novel antimitotic compound (A204197), we discovered an increase in annexin IV expression. When we examined the annexin IV protein expression level in a paclitaxel-resistant cell line (H460/T800), we found that annexin IV was also overexpressed. Interestingly a closely related protein, annexin II, was not overexpressed in H460/T800 cells. Immunostaining with either annexin II or IV antibody revealed that annexin IV was primarily located in the nucleus of paclitaxel-resistant H460/T800 cells. Short-term treatment of H460 cells with 10 nM paclitaxel for up to 4 days resulted in induction of annexin IV, but not annexin II expression. In addition, there was an increase in annexin IV staining in the nucleus starting at day 1. Furthermore, cells pretreated with 10 nM paclitaxel for 4 days resulted in cells becoming ~fivefold more resistant to paclitaxel. Transfection of annexin IV cDNA into 293T cells revealed that there was a threefold increase in paclitaxel resistance. Thus our results indicate that annexin IV plays a role in paclitaxel resistance in this cell line and it is among one of the earliest proteins that is induced in cells in response to cytotoxic stress such as antimitotic drug treatment. © 2000 Cancer Research Campaign

Keywords:

annexin, paclitaxel, drug resistance, antimitotic

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