Reduction of tumorigenesis and invasion of human breast cancer cells by whey acidic protein (WAP)

Naoko Nukumi, Tokuko Iwamori, Kiyoshi Kano, Kunihiko Naito, Hideaki Tojo

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalCancer Letters
Volume252
Issue number1
DOIs
Publication statusPublished - Jul 8 2007
Externally publishedYes

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Carcinogenesis
Breast Neoplasms
MCF-7 Cells
Breast
Epithelial Cells
whey acidic proteins
Angiopoietin-2
Amino Acid Motifs
Serine Proteinase Inhibitors
Laminin
Nude Mice
Disulfides
Estrogens
Peptide Hydrolases
Cell Proliferation
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Reduction of tumorigenesis and invasion of human breast cancer cells by whey acidic protein (WAP). / Nukumi, Naoko; Iwamori, Tokuko; Kano, Kiyoshi; Naito, Kunihiko; Tojo, Hideaki.

In: Cancer Letters, Vol. 252, No. 1, 08.07.2007, p. 65-74.

Research output: Contribution to journalArticle

Nukumi, Naoko ; Iwamori, Tokuko ; Kano, Kiyoshi ; Naito, Kunihiko ; Tojo, Hideaki. / Reduction of tumorigenesis and invasion of human breast cancer cells by whey acidic protein (WAP). In: Cancer Letters. 2007 ; Vol. 252, No. 1. pp. 65-74.
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