Estrogen Receptor β as a Possible Double-Edged Sword Molecule in Breast Cancer: A Mechanism of Alteration of Its Role by Exposure to Endocrine-Disrupting Chemicals

Biol Pharm Bull. 2021;44(11):1594-1597. doi: 10.1248/bpb.b21-00468.ABSTRACTEstrogen is essential for the growth and development of mammary glands and its signaling is associated with breast cancer growth. Estrogen can exert physiological actions via estrogen receptors α/β (ERα/β). There is experimental evidence suggesting that in ERα/β-positive breast cancer, ERα promotes tumor cell proliferation and ERβ inhibits ERα-mediated transcriptional activity, resulting in abrogation of cell growth. Therefore, ERβ is attracting attention as a potential tumor suppressor, and as a biomarker and therapeutic target in the ERα/β-positive breast cancer. Based on this information, we have hypothesized that some endocrine-disrupting chemicals (EDCs) that can perturb the balance between ERα and ERβ expression levels in breast cancer cells might have effects on the breast cancer proliferation (i.e., down-regulation of the α-type of ER). We have recently reported that 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), an active metabolite of bisphenol A, in ERα/β-positive human breast cancer significantly down-regulates ERα expression, yet stimulates cell proliferation through the activation of ERβ-mediated transcription. These results support our hypothesis by demonstrating that exposure to MBP altered the functional role of ERβ in breast cancer cells from suppressor to promoter. In contrast, some EDCs, such as Δ9-tetrahydrocannabinol and bisphenol AF, can exhibit anti-estr...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Source Type: research