title: Effect of estradiol and clomiphene citrate on Erk activation in breast cancer cells.
abstract: The mitogen-activated protein kinase (MAPK) signaling pathway plays key roles in the transmission of proliferative signals in normal and dysregulated cells. Nevertheless, some studies have shown that activation of the extracellular regulated kinases 1/2 (Erk1/2) is involved in apoptosis. In this study, we evaluate the effect of two fertilizing drugs, clomiphene citrate and estradiol, on the activation of Erk1/2 and the viability of two breast cancer cell lines, MCF-7 (hormone dependent) and BT20 (hormone independent).We show that both drugs induce Erk1/2 phosphorylation in MCF-7 and BT20 cells despite their opposite effect on cell viability. In fact, clomiphene citrate is significantly proapoptotic while estradiol promotes cell proliferation. The fact that phospho-Erk1/2 is a common element to both mechanisms suggests that specific factors deciding between proliferation and apoptosis must be operative downstream of this signaling pathway.
authors.affiliation: Centre of Biotechnology of Sfax , Sfax , Tunisia and.
authors.forename: Jihene
authors.initials: J
authors.lastname: Elloumi-Mseddi
authors.forename: Ikram
authors.initials: I
authors.lastname: Jemel-Oualha
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Beji
authors.forename: Bochra
authors.initials: B
authors.lastname: Hakim
authors.forename: Sami
authors.initials: S
authors.lastname: Aifa
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002996:Clomiphene / Q000008:administration & dosage; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis* / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D002996:Clomiphene; D004958:Estradiol; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Apoptosis; Erk activation; cell proliferation; clomiphene citrate; estradiol