title: Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells.
abstract: Estrogen replacement therapy and other unopposed estrogen treatments increase the incidence of endometrial abnormalities, including cancer. However, this effect is counteracted by the co-administration of progesterone. In the endometrium, glucose transporter (GLUT) expression and glucose transport are known to fluctuate throughout the menstrual cycle. Here, we determined the effect of estrogen and progesterone on the expression of GLUT1-4 and on the transport of deoxyglucose in Ishikawa endometrial cancer cells. Cells were incubated with estrogen, progesterone or combined estrogen and progesterone for 24 h and the effect on the expression of GLUT1-4 and on deoxyglucose transport was determined. We show that GLUT1 expression is upregulated by estrogen and progesterone individually, but that combined estrogen and progesterone treatment reverses this increase. Hormonal treatments do not affect GLUT2, GLUT3 or GLUT4 expression. Transport studies demonstrate that estrogen increases deoxyglucose transport at Michaelis-Menten constants (Kms) corresponding to GLUT1/4, an effect which disappears when progesterone is added concomitantly. These data demonstrate that different hormonal treatments differentially regulate GLUT expression and glucose transport in this endometrial cancer cell line. This regulation mirrors the role played by estrogen and progesterone on the incidence of cancer in this tissue and suggests that GLUT1 may be utilized by endometrial cancer cells to fuel their demand for increased energy requirement.
authors.affiliation: Laboratorio de Biología Celular y Molecular, MIFAB, Universidad Nacional Andrés Bello, Republica 217, Piso 4, Santiago, Chile. rmedina@unab.cl
authors.forename: Rodolfo A
authors.initials: RA
authors.lastname: Medina
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Meneses
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Vera
authors.forename: Catherine
authors.initials: C
authors.lastname: Gúzman
authors.forename: Francisco
authors.initials: F
authors.lastname: Nualart
authors.forename: Federico
authors.initials: F
authors.lastname: Rodriguez
authors.forename: Maria
authors.initials: M
authors.lastname: de los Angeles Garcia
authors.forename: Sumie
authors.initials: S
authors.lastname: Kato
authors.forename: Natalia
authors.initials: N
authors.lastname: Espinoza
authors.forename: Carolina
authors.initials: C
authors.lastname: Monsó
authors.forename: Andres
authors.initials: A
authors.lastname: Carvajal
authors.forename: Mauricio
authors.initials: M
authors.lastname: Pinto
authors.forename: Gareth I
authors.initials: GI
authors.lastname: Owen
mesh_terms: D001692:Biological Transport; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000032:analysis / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000378:metabolism*; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004967:Estrogens; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; C495692:SLC2A4 protein, human; D011374:Progesterone; D003847:Deoxyglucose