Ethanol stimulates proliferation, ERalpha and aromatase expression in MCF-7 human breast cancer cells.
It is well documented that alcohol is associated with an increased risk factor for breast carcinogenesis although the underlying mechanisms are not clearly understood. It has been reported that in vitro, the culture of estrogen receptor (ER) expressing breast cancer cells in ethanol containing medium was associated with an increase in the proliferation rate, in the ERalpha content as well as in ER transcriptional activity. Since these changes are not observed in ER negative breast cancer cells, and since alcohol intake has been associated to an increased level of circulating estrogens, we have postulated that aromatase expression could be increased following ethanol exposure. The results of our studies show a 1.3-fold increase in cell proliferation after 6 days of culture of MCF-7 cells in the presence of 0.1% ethanol. This enhanced proliferation is confirmed by the use of clonogenic assays which show a 1.5-fold increase in clonal growth in the presence of 0.1% ethanol. No statistically significant changes were observed in the presence of higher ethanol concentration (0.3%). After a 6-day exposure to 0.1% ethanol, RT-PCR analyses reveal a 1.7-fold increase in ERalpha mRNA that was not significant, whereas western blot analyses show a significant 3.3-fold increase in ERalpha content. At the same stage, RT-PCR studies demonstrate a 2.4-fold increase in aromatase mRNA level which is confirmed at the protein level by western blots performed after immuno-precipitation of the enzyme. Taken together, these results are in agreement with the involvement of ER signalling in ethanol-induced stimulation of breast cancer cell proliferation and could help to understand why alcohol consumption is associated with breast cancer risk.
Etique
Nicolas
N
EA 3442 Génétique, Signalisation, Différenciation, Faculté des Sciences, Université Henri Poincaré-Nancy I, BP 239, 54506 Vandoeuvre-lès-Nancy Cedex, France.
Chardard
Dominique
D
Chesnel
Amand
A
Merlin
Jean-Louis
JL
Flament
Stephane
S
Grillier-Vuissoz
Isabelle
I
D001141:Aromatase / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D047628:Estrogen Receptor alpha; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D000431:Ethanol; D001141:Aromatase