SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions

Abstract

Cancer cells show increased glucose uptake and utilization in comparison with their normal counterparts. Glucose transporters play an important role in glucose uptake. We previously reported the differential gene expression of the GLUT family in primary and metastatic lesions of lung cancer. To investigate the role of Na + /glucose cotransporter (SGLT) genes in cancers, we examined the levels of expression of SGLT1 and SGLT2 genes in primary lung cancers and their metastatic lesions. Ninety-six autopsy samples (35 primary lung cancers, 35 corresponding normal lung tissues, 10 metastatic liver lesions, and 16 metastatic lymph nodes) from 35 patients were analyzed for SGLT1 and SGLT2 expression by reverse transcription (RT)-polymerase chain reaction (PCR). There were no significant differences in the level of expression of either gene between the primary lung cancers and normal lung tissues. The level of SGLT1 expression in the metastatic lesions and primary lung cancers did not differ significantly. The level of SGLT2 expression was, however, significantly higher in the metastatic lesions of both the liver and lymph node than in the primary lung cancers. These results suggest that SGLT2 plays a role in glucose uptake in the metastatic lesions of lung cancer. Key words: SGLT1 -SGLT2 -Lung cancerGlucose is a basic source of energy in mammalian cells. Cancer cells show increased glucose uptake and utilization relative to their normal counterparts.1-3) Two classes of glucose transporters have been described in mammalian cells. 4,5) One class is the facilitative glucose transporter (GLUT) family, which mediates the energy-independent transport of glucose. There are five functional isoforms of GLUT (GLUT1-GLUT5). The five transporters have different functions and distribution in human tissues. The second class is the Na + /glucose cotransporter (SGLT) family, which utilizes the electrochemical sodium gradient to transport glucose against the cell's internal concentration gradient. 4,5) Two isoforms (SGLT1 and SGLT2) have been cloned in mammalian cells.6, 7) SGLT1 is strongly expressed in the small intestine, and is expressed at lower levels in the kidneys, liver, and lungs. 8) In contrast to SGLT1, the kidneys express a high level of SGLT2, and the small intestine does not. 9)Previous studies have demonstrated the overexpression of GLUT1 in various human cancers relative to normal tissues.10) In addition, increased GLUT3 expression has been found in several cancers.11) Overexpression of GLUT5 was found in breast cancers.12) On the other hand, the expression of SGLT genes in cancers has not been studied, and the role of SGLT genes is still unclear in cancers.Recently, we studied the expression of genes belonging to the GLUT family in lung cancers and their metastatic lesions.13) Our results showed the differential expression of GLUT genes in primary lung cancers and their metastatic lesions. To investigate the role of the SGLT family in cancers, we examined the expression levels of SGLT1 and SGLT2 in primary lung cancer...

Sweet talk: insights into the nature and importance of glucose transport in lung epithelium

“…SGLT1, but not SGLT2, mRNA has been identified in distal lung epithelium from adult rats [55,60], and from mouse and human whole-lung tissue [49,56]. BODEGA et al [61] recently identified SGLT protein in type I and II alveolar cells of rat and sheep lung.…”

Hyperglycaemia and pulmonary infection

“…mRNA (Ishikawa et al 2001), but not protein (Devaskar & de Mello, 1996), and GLUT2 protein (Ito et al 1998) expression have been demonstrated in non-cancerous regions of human lung obtained at autopsy from patients with primary lung carcinomas. A proposed model of glucose homeostasis in human airways is shown in Fig.…”

Tumor suppressor gene adenomatous polyposis coli downregulates intestinal transport

“…3b, c, however, SGLT1 is heavily expressed in tumor tissue suggesting that SGLT1 similarly contributes to glucose uptake of tumor cells. Expression of SGLT1 in tumor tissue has been demonstrated before [8,13,17,28,31,40,41,63]. In view of the enhanced demand of tumor cells for nutrients and the respective upregulation of glucose and amino acid transport in tumor cells [9,14,15,23,24,27,32,46,64], the upregulation of SGLT1 activity by β-catenin may contribute to the proliferation and survival of tumor cells.…”

“…β-catenin sensitive transport systems could well contribute to properties and survival of tumor cells. A variety of tumor cells do express SGLT1 [8,13,17,28,31,40,41,63] and SGLT1-dependent cellular glucose uptake may be required due to the increased energy demand of tumor cells, which is mainly covered by glucose degradation [17]. Moreover, stimulation of the Na + /H + exchanger could alkalinize the cytosol, which would facilitate flux through glycolysis [4].…”