title: Dose-dependent effect of tamoxifen in tamoxifen-resistant breast cancer             cells via stimulation by the ERK1/2 and AKT signaling pathways.
abstract: The majority of breast cancers undergo progression from an initially endocrine             responsive phenotype to an endocrine therapy-resistant phenotype, and acquired             resistance to tamoxifen (Tam) is a major clinical problem. In the present study,             we aimed to identify the function and mechanism of Tam at different concentrations             in cells with acquired Tam resistance. Estrogen-dependent MCF-7 cells were cultured             with Tam to generate Tam-resistant (TAM-R) breast cancer cells or in estrogen-free             medium to mimic the effects of clinical treatment. In addition, we analyzed the             effects of different concentrations of Tam on TAM-R cells by cell counting. Furthermore,             the crosstalk between the stimulatory G protein α subunit (Gαs) and the activation             of ERK1/2 and AKT in TAM-R cells was examined by small interfering RNA (siRNA)             and immunoblotting methods. Low-dose Tam was found to act as an estrogen agonist             via stimulation of the ERK1/2 signaling pathway, resulting in acquired resistance             to Tam, whereas high-dose Tam inhibited TAM-R cell growth by blocking the activation             of ERK1/2 and AKT. Moreover, Gαs was involved in Tam resistance in breast cancer             cells. Taken together, our study demonstrated a dose-dependent growth response             to Tam in TAM-R cells, which will promote the understanding of the importance             of the appropriate use and dosage of Tam in the clinic.
authors: Department of Oncology, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors: Li-Juan
authors: LJ
authors: Wang
authors: Su-Xia
authors: SX
authors: Han
authors: E
authors: E
authors: Bai
authors: Xia
authors: X
authors: Zhou
authors: Meng
authors: M
authors: Li
authors: Gui-Hua
authors: GH
authors: Jing
authors: Jing
authors: J
authors: Zhao
authors: An-Gang
authors: AG
authors: Yang
authors: Qing
authors: Q
authors: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004967:Estrogens / Q000819:agonists / Q000378:metabolism; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D061986:MCF-7 Cells; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D004967:Estrogens; D044385:GTP-Binding Protein alpha Subunits; D034741:RNA, Small Interfering; D013629:Tamoxifen; D051058:Oncogene Protein v-akt