Different expression patterns of Bcl-2 family genes in breast cancer by estrogen receptor status with special reference to pro-apoptotic Bak gene

Abstract

Oncogenic and anti-apoptotic Bcl-2 is expressed much less in estrogen receptor α (ERα) negative breast cancers, which show more malignant phenotypes, than ERα-positive, indicating that some other Bcl-2 family member(s) are involved in the apoptotic balance of the cancer cells. We first analyzed mRNA expression of pro-apoptotic Bak and Bax along with that of anti-apoptotic Bcl-2 and Bcl-xL, using breast cancer specimens of 27 patients. Bak mRNA was expressed much less in ERα negative breast cancers, along with reduced expression of Bcl-2. Immunostaining of sections of 108 patients confirmed the observation. Next, stable transformants of MCF-7 cells with sense Bak expression vector showed fewer colonies in soft agar compared with the parental cells, while stable introduction of antisense Bak vector enhanced colony formation at lower estradiol concentrations. The reduction of Bak may play important roles in malignant development of breast cancer to acquire estrogen independency, counteracting the reduced Bcl-2. Cell Death and Differentiation (2000) 7, 439–446

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Abbreviations

CT:

charcoal treated

E2:

17β- estradiol

ER:

estrogen receptor

GAPDH:

glyceraldehyde 3-phosphate deyhdrogenase

PRF:

phenol red free

RT–PCR:

reverse transcription polymerase chain reaction

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Acknowledgements

We thank Dr. Tomoyuki Kitagawa (Cancer Institute) for apropos advice. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, Scientific Research Expenses for Health and Welfare Programs and the Foundation for the Promotion of Cancer Research, and by 2nd-Term Comprehensive 10-year Strategy for Cancer Control.

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Correspondence to H Eguchi.

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Edited by CJ Thiele

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Eguchi, H., Suga, K., Saji, H. et al. Different expression patterns of Bcl-2 family genes in breast cancer by estrogen receptor status with special reference to pro-apoptotic Bak gene. Cell Death Differ 7, 439–446 (2000) doi:10.1038/sj.cdd.4400675

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Keywords

  • breast cancer
  • Bak
  • apoptosis
  • estrogen receptor

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