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KMID : 0380020160310010052
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Korean Journal of Biotechnology and Bioengineering
2016 Volume.31 No. 1 p.52 ~ p.57
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Silencing of Mutant p53 Leads to Suppression of Human Breast Xenograft Tumor Growth in vivo
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Park Won-Ick
Park Se-Ra
Park Hyun-Joo
Bae Yun-Hee
Ryu Hyun-Su
Jang Hye-Ock
Bae Moon-Kyoung
Bae Soo-Kyung
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Abstract
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Mutant p53 (R280K) is highly expressed in MDAMB- 231 triple-negative human breast cancer cells. Currently, we reported the role of mutant p53-R280K in mediating the survival of MDA-MB-231 cells in vitro. The present study was undertaken to determine whether mutant p53-R280K affects breast cancer cell growth in vivo. To this end, we used small interfering RNA to knockdown the level of mutant p53- R280K in MDA-MB-231 cells. Silencing of mutant p53- R280K in MDA-MB-231 cells causes substantial tumor regression of established xenografts in vivo. In xenograft model for breast cancer, silencing of mutant p53-R280K in MDAMB- 231 cells significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in mutant p53-R280K silenced tumors compared to control. Our data indicate that mutant p53-R280K has an important role in mediating tumor growth of MDA-MB-231 cells in vivo. Taken together, this study suggests that endogenous 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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Mutant p53, Breast cancer, Apoptosis, Xenograft tumor model
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