Inhibitory function of whey acidic protein in the cell-cycle progression of mouse mammary epithelial cells (EpH4/K6 cells).
Although the biological role for whey acidic protein (WAP) in milk has been suggested, its true function is not known. This paper describes evidence for WAP function in the cell-cycle progression of EpH4/K6 (EpH4), mammary epithelial cells in vitro. The forced expression of exogenous WAP significantly impaired the proliferation of EpH4 cells, whereas it did not affect that of NIH3T3 cells. Apoptosis was not enhanced in the EpH4 cells with stable expression of WAP (WAP-clonal EpH4 cells). The analyses of BrdU incorporation revealed that forced WAP expression significantly reduced incorporation of BrdU in WAP-clonal EpH4 cells compared with control cells transfected with empty plasmid. Among G1 cyclins, the level expression of cyclins D1 was significantly lower in the WAP-clonal EpH4 cells than in control cells. The inhibitory action of WAP on the proliferation of EpH4 cells was enhanced by the presence of extracellular matrix (ECM), but not by the presence of a single component comprising ECM. The cultured medium of WAP-clonal EpH4 cells inhibited the proliferation of control cells without WAP expression. The present results indicate that WAP plays a negative regulatory role in the cell-cycle progression of mammary epithelial cells through an autocrine/paracrine mechanism.
Laboratory of Applied Genetics, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Kayoko
K
Ikeda
Naoko
N
Nukumi
Tokuko
T
Iwamori
Megumi
M
Osawa
Kunihiko
K
Naito
Hideaki
H
Tojo
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D015870:Gene Expression; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008894:Milk Proteins / Q000235:genetics*; D019899:Paracrine Communication / Q000502:physiology
D056741:Cyclin D; D016213:Cyclins; D016326:Extracellular Matrix Proteins; D008894:Milk Proteins; C024471:whey acidic proteins