Journal of Dairy Research

Effects of retinoids on proliferation and plasminogen activator expression in a bovine mammary epithelial cell line

Federica Cheli a1c1, Ioannis Politis a2, Luciana Rossi a1, Eleonora Fusi a1 and Antonella Baldi a1
a1 Department of Veterinary Science and Technology for Food Safety, University of Milan, Milan, Italy 20134
a2 Department of Animal Production, Agricultural University of Athens, Athens, Greece 11855

Article author query
cheli f   [PubMed][Google Scholar] 
politis i   [PubMed][Google Scholar] 
rossi l   [PubMed][Google Scholar] 
fusi e   [PubMed][Google Scholar] 
baldi a   [PubMed][Google Scholar] 


Effects of two natural (retinol and retinoic acid, RA) and one synthetic N-(4-hydroxyphenyl) retinamide (4-HPR) retinoids on proliferation and expression of urokinase-plasminogen activator (u-PA) by bovine mammary epithelial cells were examined. The BME-UV1 established bovine mammary epithelial cell line was used as a model system. All retinoids tested (retinol, RA and 4-HPR) were effective inhibitors of cell proliferation. When cells were cultured in the absence of fetal bovine calf serum (FBCS), inhibition occurred at concentrations as low as 1 nM for all retinoids tested. The effect of retinoids on cell proliferation was not dose-related when cells were cultured in the absence of FBCS. All retinoids (retinol, RA, 4-HPR), when used in the range 1 nM–10 μM (noncytotoxic concentrations), were equally effective and had identical inhibition patterns. Inhibition of cell proliferation by RA was apparent by 6 h and was higher after 24 h in culture. In contrast, when cells were cultured in the presence of FBCS, the effect of RA and retinol on cell proliferation was dose-related. RA and retinol inhibited cell proliferation (P<0·01) when added to the culture medium in concentrations as low as 10 nM and 100 nM, respectively. 4-HPR was inhibitory (P<0·01) in concentrations as low as 1 nM. Higher concentrations of 4-HPR in the range 1 nM–1 μM had no further effect on cell proliferation. None of the retinoids tested, when added to cultures in the presence or absence of FBCS, could completely arrest cell proliferation at noncytotoxic concentrations. RA at 1 μM inhibited (P<0·05) insulin or IGF-I-induced cell proliferation but had no effect (P>0·05) on u-PA mRNA levels or u-PA activity. Furthermore, RA inhibited cell proliferation in the presence of FBCS but had no effect (P>0·05) on u-PA mRNA levels. Thus, retinoids are effective inhibitors of bovine mammary epithelial cell proliferation and this growth inhibition does not seem to correlate with any changes in u-PA mRNA or u-PA activity.

(Received November 4 2002)
(Accepted December 12 2002)

Key Words: Retinoids; bovine mammary epithelial cells; urokinase-plasminogen activator.

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