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KMID : 0381120140360020171
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Genes and Genomics
2014 Volume.36 No. 2 p.171 ~ p.178
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Gain-of-function mutant p53-R280K mediates survival of breast cancer cells
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Bae Yun-Hee
Shin Jong-Myung
Park Hyun-Joo
Jang Hye-Ock
Bae Moon-Kyoung
Bae Soo-Kyung
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Abstract
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Missense mutations in TP53 resulting in the expression of p53-R175H, p53-R273H, or p53-R280K are frequently detected in human breast cancer. Currently, the role of mutant p53-R280K in breast cancer is relatively unknown, and therefore, the present study analyzed the function of mutant p53-R280K in breast cancer cell growth. To this end, we used small interfering RNA to study the role of mutant p53-R280K in MDA-MB-231 cells, which endogenously express the mutant protein. We found that curcumin induced apoptosis in MDA-MB-231 cells and downregulated mutant p53-R280K. We also observed that knockdown of mutant p53 by small interfering RNA induced apoptosis in MDA-MB-231 cells. Curcumin-induced apoptosis was further enhanced by the overexpression of wild-type p53, but was decreased by mutant p53-R280K overexpression. Our findings indicate that mutant p53-R280K has an important role in mediating the survival of triple-negative breast cancer MDA-MB-231 cells. Furthermore, this study suggests mutant p53-R280K could be used as a therapeutic target for breast cancer cells harboring this TP53 missense mutation.
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KEYWORD
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Apoptosis, Breast cancer cells, Curcumin, Mutant p53
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