TY - JOUR
T1 - Reduction of tumorigenesis and invasion of human breast cancer cells by whey acidic protein (WAP)
AU - Nukumi, Naoko
AU - Iwamori, Tokuko
AU - Kano, Kiyoshi
AU - Naito, Kunihiko
AU - Tojo, Hideaki
N1 - Funding Information:
We thank Dr. S. Higashiyama (Ehime University School of Medicine, Japan) for providing us with MDA-MB-453 cells. This work was supported in part by Grants-in-Aid for Scientific Research (B) (Nos. 14360173 and 14360174) from the Ministry of Education, Science, Sports, and Culture of Japan. This work was also supported in part by Grants-in-Aid from Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (No. 16-11104).
PY - 2007/7/8
Y1 - 2007/7/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.canlet.2006.12.005
DO - 10.1016/j.canlet.2006.12.005
M3 - Article
C2 - 17215074
AN - SCOPUS:34248335487
SN - 0304-3835
VL - 252
SP - 65
EP - 74
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -
