title: PPARγ agonists target aromatase via both PGE2 and BRCA1.
abstract: Obesity is a well-recognized risk factor for postmenopausal breast cancer. Although the underlying mechanisms are not clearly defined, aromatase is thought to play a pivotal role in connecting obesity-associated inflammation with postmenopausal breast cancer. It has been well established that both the proinflammatory prostaglandin E(2) (PGE(2)) and the BRCA1 tumor-suppressor gene regulate aromatase expression. In this issue of the journal (beginning on p. 1183), Subbaramaiah and colleagues improve our understanding of the molecular mechanisms by which PPARγ inhibits aromatase expression. They found that pioglitazone, a PPARγ agonist, inhibited aromatase expression by inhibition of PGE(2) signaling and upregulation of BRCA1. Their findings provide potential targets for preventing or treating obesity-related breast cancer.
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Margalit
authors.forename: Dingzhi
authors.initials: D
authors.lastname: Wang
authors.forename: Raymond N
authors.initials: RN
authors.lastname: Dubois
mesh_terms: D001141:Aromatase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D001141:Aromatase; D015232:Dinoprostone; D000077205:Pioglitazone