CHANGES IN GLUCOSE-TRANSPORT ASSOCIATED WITH MALIGNANT TRANSFORMATION(REVIEW)

It has been known for many years that changes in glucose metabolism ar e associated with neoplasia and research on this phenomenon has focuse d on the enhancement of glucose transport by malignant transformation. Viral transformation of fibroblastic cells provided the first system in which this enhancement could be studied using non-metabolizable glu cose analogs. Kinetic and immunological analyses demonstrated that thi s was due to an increase in the number of glucose carriers at the plas ma membrane. In the last 10 years glucose transporter (GLUT) proteins have been characterized by molecular cloning allowing direct examinati on of the molecular mechanisms of induction of transporter expression. GLUT proteins are a family of at least six separate isoforms which ar e encoded by distinct genes and differ in tissue distribution and regu lation. Two of these isoforms, GLUT1 and GLUT3, are responsible for th e changes associated with malignant transformation. The processes invo lved in the disregulation of these isoforms in the transformation of c ultured fibroblastic and hematopoietic cells are described. Analysis o f clinical samples indicates that GLUT1 and GLUT3 are often overexpres sed in malignant tissue where they may aid tumor growth.