title: Differential subcellular distribution of glucose transporters GLUT1-6 and GLUT9 in human cancer: ultrastructural localization of GLUT1 and GLUT5 in breast tumor tissues.
abstract: It has been proposed that the enhanced metabolic activity of tumor cells is accompanied by an increased expression of facilitative hexose transporters (GLUTs). However, a previous immunohistochemical analysis of GLUT1 expression in 154 malignant human neoplasms failed to detect the GLUT1 isoform in 87 tumors. We used 146 normal human tissues and 215 tumor samples to reassess GLUT1 expression. A similar number of samples were used to compare the expression of GLUT2-6 and 9. The classical expression of GLUT1-5 in different normal human tissues was confirmed, however, we were unable to detect GLUT2 in human pancreatic islet cells. GLUT6 was principally detected in testis germinal cells and GLUT9 was localized in kidney, liver, heart, and adrenal. In tumor samples, GLUT1, 2, and 5 were the main transporters detected. GLUT1 was the most widely expressed transporter, however, 42% of the samples had very low-to-negative expression levels. GLUT2 was detected in 31% of the samples, being mainly expressed in breast, colon, and liver carcinoma. GLUT5 was detected in 27% of breast and colon adenocarcinoma, liver carcinoma, lymphomas, and testis seminoma samples. In situ RT-PCR and ultrastructural immunohistochemistry confirmed GLUT5 expression in breast cancer. GLUT6 and 9 are not clearly over-expressed in human cancer. The extensive expression of GLUT2 and 5 (glucose/fructose and fructose transporters, respectively) in malignant human tissues indicates that fructose may be a good energy substrate in tumor cells. Our functional data obtained in vitro in different tumor cells support this hypothesis. Additionally, these results suggest that fructose uptake could be used for positron emission tomography imaging and, may possibly represent a novel target for the development of therapeutic agents in different human cancers.
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160C, Concepción, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Godoy
authors.forename: Viviana
authors.initials: V
authors.lastname: Ulloa
authors.forename: Federico
authors.initials: F
authors.lastname: Rodríguez
authors.forename: Karin
authors.initials: K
authors.lastname: Reinicke
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Yañez
authors.forename: María de los Angeles
authors.initials: Mde L
authors.lastname: García
authors.forename: Rodolfo A
authors.initials: RA
authors.lastname: Medina
authors.forename: Mónica
authors.initials: M
authors.lastname: Carrasco
authors.forename: Sofía
authors.initials: S
authors.lastname: Barberis
authors.forename: Tamara
authors.initials: T
authors.lastname: Castro
authors.forename: Fernando
authors.initials: F
authors.lastname: Martínez
authors.forename: Ximena
authors.initials: X
authors.lastname: Koch
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Vera
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Poblete
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Figueroa
authors.forename: Bruno
authors.initials: B
authors.lastname: Peruzzo
authors.forename: Fernando
authors.initials: F
authors.lastname: Pérez
authors.forename: Francisco
authors.initials: F
authors.lastname: Nualart
mesh_terms: D000818:Animals; D001706:Biopsy; D001940:Breast / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D006262:Health; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D016253:Microscopy, Immunoelectron; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D009928:Organ Specificity; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D051246:Glucose Transport Proteins, Facilitative