کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2115214 | 1084581 | 2007 | 10 صفحه PDF | دانلود رایگان |
Whey acidic protein (WAP) is a major component of whey, which has two or three WAP motif domains characterized by a four-disulfide core (4-DSC) structure similar to the serine protease inhibitor. We have previously found that WAP inhibits the proliferation of mammary epithelial cells in vitro and in vivo [N. Nukumi, K. Ikeda, M. Osawa, T. Iwamori, K. Naito, H. Tojo, Regulatory function of whey acidic protein in the proliferation of mouse mammary epithelial cells in vivo and in vitro, Dev. Biol. 274 (2004) 31–44]. We report herein that WAP also reduces the progression of human breast cancer cells (MCF-7 and MDA-MB-453 cells). We have demonstrated that the forced expression of WAP in MCF-7 cells reduces the proliferation in either the presence or absence of estrogen. The tumor progression of WAP-expressing MCF-7 cells in nude mice is significantly suppressed more than that of mock-MCF-7 cells following the reduced expression of angiopoietin-2 gene. We have confirmed that the invasive activity of breast cancer cells is reduced to ∼30% of that of mock cells by the forced expression of exogenous WAP through its inhibition of degradation of laminin. These data suggest that WAP has a protease-inhibitory function on the progression of breast cancer cells. It is therefore possible to utilize WAP as therapeutic protein against tumorigenesis of breast cancer.
Journal: Cancer Letters - Volume 252, Issue 1, 8 July 2007, Pages 65–74