Interplay of genes regulated by estrogen and diindolylmethane in breast cancer cell lines.
Diindolylmethane (DIM), a biologically active congener of indole-3-carbinol (I3C) derived from cruciferous vegetables, is a promising agent for the prevention of estrogen-sensitive cancers. Both DIM and estrogen affect transcription of genes by binding receptors, such as aryl hydrocarbon receptor (AhR) or estrogen receptors (ER). Gene regulation by DIM and estradiol (E2) can be very complex. While DIM typically binds the AhR, this complex can directly associate with the ER, recruit co-activators that bind to estrogen-responsive promoters, and activate transcription. Alternately, DIM can bind the ER directly. In this study, we have analyzed gene expression using microarray profiling and quantitative real time-polymerase chain reaction in MCF7 breast cancer cells treated with E2 (1 nM) or DIM (25 microM) alone or in combination for 16 h. The interplay of E2 and DIM was reflected in the expression of a subset of genes (<90) in which the combination of E2 and DIM acted either additively or antagonistically to alter gene expression.
Mulvey
Laura
L
Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
Chandrasekaran
Alamelu
A
Liu
Kai
K
Lombardi
Sarah
S
Wang
Xue-Ping
XP
Auborn
Karen J
KJ
Goodwin
Leslie
L
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D016588:Anticarcinogenic Agents; D004967:Estrogens; D007211:Indoles; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; C016392:3,3'-diindolylmethane