Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells.
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.
Medina
Rodolfo A
RA
Laboratorio de Biología Celular y Molecular, MIFAB, Universidad Nacional Andrés Bello, Republica 217, Piso 4, Santiago, Chile. rmedina@unab.cl
Meneses
Ana Maria
AM
Vera
Juan Carlos
JC
Gúzman
Catherine
C
Nualart
Francisco
F
Rodriguez
Federico
F
de los Angeles Garcia
Maria
M
Kato
Sumie
S
Espinoza
Natalia
N
Monsó
Carolina
C
Carvajal
Andres
A
Pinto
Mauricio
M
Owen
Gareth I
GI
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
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