Effects of resveratrol on the expression of a panel of genes interacting with the BRCA1 oncosuppressor in human breast cell lines.
BACKGROUND
trans-Resveratrol, or 3,5,4'trihydroxy-trans-stilbene, is a polyphenolic compound that seems to provide a protective effect against several types of cancer, notably breast cancer. Through its phytoestrogenic properties it regulates the expression of hormone-dependent genes, such as the oncosuppressor BRCA1, in breast cells. This gene is involved in the majority of hereditary breast cancer, as well as sporadic cancers.


METHODS
We used three human breast tumor cell lines (HBL100, MCF7 and MBA-MB-231) and one breast cell line (MCF10a) derived from a fibrocystic disease to study in vitro the effect of resveratrol on the transcription of a group of genes whose proteins interact in different pathways with BRCA1. BRCA1, BRCA2, ER alpha, ER beta, p53, p21(waf1/cip1), CBP/P300, RAD51, pS2 and Ki67 mRNA were quantified using real-time quantitative RT-PCR with an ABI 7700 apparatus.


RESULTS
Resveratrol modulated the expression of these genes in a pattern dependent on the status of alpha and beta estrogen receptors. These results show that resveratrol regulates gene expression via the estrogen receptor pathway and also an undetermined pathway.


CONCLUSIONS
Thus, resveratrol seems to have an effect on breast tumor cell lines, on a fibrocystic cell line by affecting several factors regulating the function of BRCA1.
Le Corre
Ludovic
L
Laboratoire d'Oncologie Moléculaire, Centre Jean Perrin, INSERM UMR 484-UdA, 58 rue Montalembert B.P.392, 63011 Clermont-Ferrand Cedex 1, France.
Fustier
Pierre
P
Chalabi
Nasséra
N
Bignon
Yves-Jean
YJ
Bernard-Gallon
Dominique
D
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005348:Fibrocystic Breast Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D013267:Stilbenes; D025521:Tumor Suppressor Proteins; D000077185:Resveratrol