Klf10 induces cell apoptosis through modulation of BI-1 expression and Ca2+ homeostasis in estrogen-responding adenocarcinoma cells

Ching Fang Hsu, Chia Ling Sui, Wen Chi Wu, Jun Jie Wang, Diane H A Yang, Yu Chi Chen, Winston C Y Yu, Hung Shu Chang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Estrogen stimulates cell growth and inhibits apoptosis through estrogen receptor-mediated mechanisms in many cell types. Remarkably, there is another dimension to estrogen action by which apoptosis is induced in breast cancer cells. While these mechanisms are not yet completely understood, finding the molecules involved has paved the way for the development of a new drug group. Using ChIP-chip, we have demonstrated that Klf10, a Krüppel-like zinc finger transcription factor, which was induced in response to estrogen, directly modulates the transcription of BI-1 (Bax inhibitor-1; also called the testis-enhanced gene transcript, TEGT). Eventually, the estrogen induced Klf10 and then suppresses BI-1 transcription. The estrogen/Klf10/BI-1 interrelationship was further confirmed using BI-1 promoter and EMSA assays. The estrogen-elicited reduction of BI-1 promoter activity was significantly reversed when the Klf10 binding element was mutated to abolish Klf10 binding. A si-Klf10 antisense-oligo nucleotide was also able to restore BI-1 promoter activity to its pre-estrogen-treatment level. BI-1 is known to regulate stress via the endoplasmic reticulum; in this context down-regulation of BI-1 is able to cause Ca2+ release and trigger an apoptosis pathway in breast cancer. In our study, Klf10 not only suppressed cellular BI-1 expression but also increased the cytosolic Ca2+ concentration, eventually causing apoptotic cell death. Based on these results, we suggest the pathway by which estrogen induces apoptosis is possibly through an up-regulation of Klf10 that decreases BI-1 and finally increases the concentration of cytoplasmic calcium.

Original languageEnglish
Pages (from-to)666-673
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume43
Issue number4
DOIs
Publication statusPublished - Apr 2011
Externally publishedYes

Fingerprint

Estrogens
Adenocarcinoma
Homeostasis
Modulation
Apoptosis
Transcription
1-(7-(2-hydroxyethyl)dodecahydro-3a-methyl-1H-benz(e)inden-3-yl)ethanone
Breast Neoplasms
Endoplasmic Reticulum Stress
Zinc Fingers
Cell growth
Cell death
Estrogen Receptors
Testis
Zinc
Assays
Cell Death
Transcription Factors
Up-Regulation
Down-Regulation

Keywords

  • BI-1
  • Breast cancer
  • Ca homeostasis
  • Estrogen
  • Klf10

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Klf10 induces cell apoptosis through modulation of BI-1 expression and Ca2+ homeostasis in estrogen-responding adenocarcinoma cells. / Hsu, Ching Fang; Sui, Chia Ling; Wu, Wen Chi; Wang, Jun Jie; Yang, Diane H A; Chen, Yu Chi; Yu, Winston C Y; Chang, Hung Shu.

In: International Journal of Biochemistry and Cell Biology, Vol. 43, No. 4, 04.2011, p. 666-673.

Research output: Contribution to journalArticle

Hsu, Ching Fang ; Sui, Chia Ling ; Wu, Wen Chi ; Wang, Jun Jie ; Yang, Diane H A ; Chen, Yu Chi ; Yu, Winston C Y ; Chang, Hung Shu. / Klf10 induces cell apoptosis through modulation of BI-1 expression and Ca2+ homeostasis in estrogen-responding adenocarcinoma cells. In: International Journal of Biochemistry and Cell Biology. 2011 ; Vol. 43, No. 4. pp. 666-673.
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AU - Chen, Yu Chi

AU - Yu, Winston C Y

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