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Anti‐apoptotic effect of the basic helix‐loop‐helix (bHLH) transcription factor DEC2 in human breast cancer cells
Author(s) -
Liu Yang,
Sato Fuyuki,
Kawamoto Takeshi,
Fujimoto Katsumi,
Morohashi Satoko,
Akasaka Harue,
Kondo Jun,
Wu Yunyan,
Noshiro Mitsuhide,
Kato Yukio,
Kijima Hiroshi
Publication year - 2010
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2010.01381.x
Subject(s) - biology , basic helix loop helix , apoptosis , transcription factor , breast cancer , helix (gastropod) , human breast , cancer research , microbiology and biotechnology , cancer , genetics , dna binding protein , gene , ecology , snail
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‐α (TNF‐α) 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‐α 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‐α. 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.