title: ER beta inhibits proliferation and invasion of breast cancer cells.
abstract: Recent studies indicate that the expression of ER beta in breast cancer is lower than in the normal breast, suggesting that ER beta could play an important role in carcinogenesis. To investigate this hypothesis, we engineered ER-negative MDA-MB-231 (human breast cancer cells) to reintroduce either ER alpha or ER beta protein with an adenoviral vector. In these cells, ER beta (as ER alpha) expression was monitored using RT-PCR and Western blot. ER beta protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of E2. ER beta and ER alpha induced the expression of several endogenous genes such as pS2, TGF alpha, or the cyclin kinase inhibitor p21 but, in contrast to ER alpha, ER beta was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ER alpha and ER beta estrogen-induced activities. ER beta inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ER alpha inhibition of proliferation is hormone dependent. Moreover, ER beta and ER alpha decreased cell motility and invasion. Our data bring the first evidence that ER beta is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ER beta expression could be one of the events leading to the development of breast cancer.
authors.affiliation: INSERM U540 Molecular and Cellular Endocrinology of Cancers, 34090 Montpellier, France. lazennec@u540.montp.inserm.fr
authors.forename: G
authors.initials: G
authors.lastname: Lazennec
authors.forename: D
authors.initials: D
authors.lastname: Bresson
authors.forename: A
authors.initials: A
authors.lastname: Lucas
authors.forename: C
authors.initials: C
authors.lastname: Chauveau
authors.forename: F
authors.initials: F
authors.lastname: Vignon
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000502:physiology; D005822:Genetic Vectors; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D000090063:Proto-Oncogene Mas; D011960:Receptors, Estrogen / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011960:Receptors, Estrogen