Anti-apoptotic effect of the basic helix-loop-helix (bHLH) transcription factor DEC2 in human breast cancer cells.

Abstract

DEC1 (BHLHB2/Stra13/Sharp2) and DEC2 (BHLHB3/Sharp1) are basic helix-loop-helix (bHLH) transcription factors that are involved in circadian rhythms, differentiation and the responses to hypoxia. We examined whether DEC1 and DEC2 are involved in apoptosis regulation, in human breast cancer MCF-7 cells. We found that siRNA-mediated knockdown of DEC2 resulted in marked enhancement of apoptosis compared with that in control cells transfected with nonspecific siRNA. However, knockdown of DEC1 by siRNA did not affect cell survival. Knockdown of DEC2 affected the expression of mRNA or proteins related to apoptosis, such as Fas, c-Myc, caspase-8, poly (ADP-ribose) polymerase (PARP) and Bax. We also showed that tumor necrosis factor-alpha (TNF-alpha) up-regulates the expression of DEC1 and DEC2. DEC2 over-expression caused by the transfection of an expression vector reduced the amounts of cleaved PARP and caspase-8 induced by TNF-alpha treatment, whereas DEC1 over-expression increased it. Finally, we revealed that treatment with double knockdown against both DEC1 and DEC2 decreased the amounts of cleaved PARP and caspase-8 induced by DEC2 siRNA with or without TNF-alpha. These data indicate that DEC2 has an anti-apoptotic effect, whereas DEC1 has a pro-apoptotic effect, which are involved in the balance of survival of human breast cancer MCF-7 cells.

• Authors: Yang Liu, Fuyuki Sato, Takeshi Kawamoto, Katsumi Fujimoto, Satoko Morohashi, Harue Akasaka, Jun Kondo, Yunyan Wu, Mitsuhide Noshiro, Yukio Kato, Hiroshi Kijima
• Journal: Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 15 Issue 4 Pg. 315-25 (Apr 01 2010) ISSN: 1365-2443 [Electronic] England
• PMID: 20236182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• RNA, Messenger
• RNA, Small Interfering
• Transcription Factors
• Tumor Necrosis Factor-alpha
• Tumor Suppressor Proteins
• Adenosine Diphosphate Ribose
• Caspase 8

Topics

• Adenosine Diphosphate Ribose (genetics, metabolism)
• Apoptosis (genetics)
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Breast Neoplasms (genetics)
• Caspase 8 (genetics, metabolism)
• Cell Line, Tumor
• Circadian Rhythm (genetics, physiology)
• Female
• Humans
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Transcription Factors (genetics, metabolism, physiology)
• Transfection
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)