title: Whey acidic protein (WAP) depresses the proliferation of mouse (MMT) and human (MCF-7) mammary tumor cells.
abstract: We previously reported that the enforced expression of exogenous whey acidic protein (WAP) significantly inhibited the proliferation of mouse mammary epithelial cells (HC11 and EpH4/H6 cells). This paper presents the first evidence that WAP also depresses the proliferation of mammary tumor cells from mouse (MMT cells) and human (MCF-7 cells). We established WAP-clonal MMT and MCF-7 cell lines, and confirmed the secretion of WAP from the WAP-clonal cells into culture medium. The enforced expression of WAP significantly inhibited the proliferation of MMT and MCF-7 cells in in vitro culture. FACScan analyses revealed that G0/G1 phase cell-cycle progression was disordered and elongated in the WAP-clonal MMT and MCF-7 cells compared to that of the control cells. The expression of cyclin D1 was significantly decreased in the WAP-clonal MMT and MCF-7 cells, suggesting that progression from the G1 to the S phase was delayed in the WAP-clonal cells. The present results indicate that WAP plays a negative regulatory role in the cell-cycle progression of mammary tumor cells via a paracrine mechanism.
authors.affiliation: Laboratory of Applied Genetics, Graduate School of Agricultural and Life Sciences, University of Tokyo, Japan. aa37123@mail.ecc.u-tokyo.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Nukumi
authors.forename: Tokuko
authors.initials: T
authors.lastname: Iwamori
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Naito
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tojo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D008894:Milk Proteins; C024471:whey acidic proteins; D012313:RNA