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Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

Present study was aimed to investigate the relationship of p53 mutation status with response to docetaxel in breast cancers. In addition, attempts were made to identify the genes differentially expressed between p53-wild and p53-mutated breast tumors and to study their relationship with response to docetaxel.

Methods

Mutational analysis of p53 was done in 50 breast tumor samples obtained from primary breast cancer patients (n = 33) and locally recurrent breast cancer patients (n = 17) before docetaxel therapy. Response to docetaxel was evaluated clinically. Gene expression profiling (n = 2,412) was conducted by adapter-tagged competitive-PCR in 186 tumor samples, which were also analyzed in their p53 mutational status in order to identify the differentially expressed genes according to p53 mutation status and their relationship with response to docetaxel.

Results

Response rate of p53-mutated tumors (44%) was lower than that of p53-wild tumors (62%) though there was no statistical significance (P = 0.23). Of 2412 genes, mRNA expression of 13 genes was significantly different between p53-wild and p53-mutated tumors. Of these 13 genes, mRNA expression of CCT5, RGS3,␣and YKT6 was significantly up-regulated in p53-mutated tumors and associated with a low response rate to docetaxel. Treatment of MCF-7 cells with siRNA specific for CCT5, RGS3, or YKT6 resulted in a significant enhancement of docetaxel-induced apoptosis.

Conclusions

CCT5, RGS3, and YKT6 mRNA expressions, which are up-regulated in p53-mutated breast tumors, might be implicated in resistance to docetaxel and clinically useful in identifying the subset of breast cancer patients who may or may not benefit from docetaxel treatment.

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Abbreviations

ER:

Estrogen receptor

RGS3:

Regulator of G-protein signaling 3

CCT5:

Chaperonin containing TCP1 Subunit 5 (epsilon)

YKT6:

Soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein Ykt6

siRNA:

Small interfering RNA

DHPLC:

Denaturing high performance liquid chromatography

ATAC-PCR:

Adapter-tagged competitive polymerase chain reaction

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Acknowledgments

This work was supposed in part by a Grant-in-aid for Scientific Research on priority Areas (No. 12217075) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Asako Ooe, Kikuya Kato & Shinzaburo Noguchi

  2. Osaka Medical Center for Cancer and Cardiovascular Diseases, Research Institute, 1-3-2 Nakamichi, Higashinari-ku, 537-8511, Osaka, Japan

    Kikuya Kato

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  1. Asako Ooe
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Correspondence to Shinzaburo Noguchi.

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Ooe, A., Kato, K. & Noguchi, S. Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers. Breast Cancer Res Treat 101, 305–315 (2007). https://doi.org/10.1007/s10549-006-9293-x

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  • DOI: https://doi.org/10.1007/s10549-006-9293-x

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