title: Lack of effect of the procarcinogenic 17β-estradiol on nutrient uptake by the MCF-7 breast cancer cell line.
abstract: Breast cancer is one of the most frequent cancers in the population, especially in older women. Estrogen is known to be a key hormone in the development and progression of mammary carcinogenesis. In this study, we investigated if the procarcinogenic effect of 17β-estradiol (E2) in breast cancer MCF-7 cells is dependent on changes in glucose or folic acid cellular uptake. The effect of E2 on uptake of3H-deoxy-d-glucose,3H-folic acid, cell proliferation (3-thymidine incorporation assay), culture growth (sulforhodamine B assay), viability (lactate dehydrogenase activity assay), lactate production and migration capacity (injury assay) was evaluated. E2 (48h; 100nM) increased culture growth (16%), proliferation rate (24%), cellular viability (36%) and lactate production (38%). In contrast, E2 did not significantly affect the migration capacity of MCF-7 cells. The pro-proliferative, but not the cytoprotective effect of E2 was found to be ERβ-dependent. The polyphenols rutin and caffeic acid were not able to counteract the effect of E2 upon cell proliferation and viability. Uptake of3H-deoxy-d-glucose was not affected by E2, either in the absence or presence of GLUT inhibitors (cytochalasin B plus phloridzin). Moreover, E2 did not change GLUT1 mRNA levels. Finally,3H-folic acid uptake was also not affected by E2, both in the absence and presence of the RFC1 inhibitor, methotrexate. The pro-proliferative and cytoprotective effects of E2 are not dependent neither of stimulation of glucose cellular uptake (both GLUT and non-GLUT-mediated) nor of stimulation of folic acid uptake (both RFC1-and non-RFC1-mediated).
authors.affiliation: Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; Institute for Research and Innovation in Health Sciences (I3S), University of Porto, Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Nunes
authors.affiliation: Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; Institute for Research and Innovation in Health Sciences (I3S), University of Porto, Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Silva
authors.affiliation: Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; Institute for Research and Innovation in Health Sciences (I3S), University of Porto, Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Correia-Branco
authors.affiliation: Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal; Institute for Research and Innovation in Health Sciences (I3S), University of Porto, Porto, Portugal. Electronic address: fmartel@med.up.pt.
authors.forename: F
authors.initials: F
authors.lastname: Martel
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D002109:Caffeic Acids / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000009:adverse effects*; D005260:Female; D005502:Food / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D059808:Polyphenols / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology
chemical_list: D002109:Caffeic Acids; D051272:Glucose Transporter Type 1; D059808:Polyphenols; D012333:RNA, Messenger; D004958:Estradiol; D012431:Rutin; D005947:Glucose; C040048:caffeic acid
keywords: Breast cancer cells; Estrogen receptors; Folic acid uptake; GLUT; Glucose uptake; Polyphenols; RFC1