Differential Expression of Facilitative Glucose Transporter (<i>GLUT</i>) Genes in Primary Lung Cancers and Their Liver Metastases

Kurata, Takeshi; Oguri, Tetsuya; Isobe, Takeshi; Ishioka, Shinichi; Yamakido, Michio

doi:10.1111/j.1349-7006.1999.tb00702.x

Cited by 82 publications

(63 citation statements)

References 25 publications

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“…We showed that primary lung tumors expressed a significantly higher level of GLUT1 than normal lung tissues, 13) although the expression of GLUT3 and GLUT5 in the primary tumors and normal lung tissues did not significantly differ. Taking these results and the findings of other reports into consideration, we concluded that GLUT1 may play a major role in glucose uptake in primary lung cancer cells.…”

Section: Discussionmentioning

confidence: 70%

“…Although we have reported that the levels of GLUT3 and GLUT5 expression were significantly higher in the liver metastases of lung cancer than in the primary lung cancers, 13) we are not aware of other reports describing the differential expression of the GLUT or SGLT genes in primary lung cancers and their metastatic lesions. In this study, we found that the metastatic lesions of lung cancer expressed a significantly higher level of SGLT2 than the primary lung cancers.…”

Section: Discussionmentioning

confidence: 78%

“…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 cancers and their metastatic lesions.…”

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confidence: 82%

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SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions

Ishikawa

Oguri

Isobe

et al. 2001

Japanese Journal of Cancer Research

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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...

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 78%

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SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions

Ishikawa

Oguri

Isobe

et al. 2001

Japanese Journal of Cancer Research

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“…Therefore, GLUT-1 expression may be a suitable marker of hypoxia and glucose metabolism, measured simply and cost-effectively as part of the routine histological assessment of tumors (9,10). GLUT-1 has been immunohistochemically detected in a variety of malignant tissues, including tumors of the breast, thyroid, head and neck, bladder and lung (11)(12)(13)(14)(15). In all cases, the tumor expression was increased as compared to that of the corresponding normal tissues.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy

et al. 2010

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Abstract. This study aimed to investigate whether glucose transporter-1 (GLUT-1) expression in a pretreatment esophageal cancer biopsy was predictive of clinical outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). A total of 25 patients with esophageal cancer treated with concurrent CRT were reviewed. Radiotherapy was administered up to total doses of 40-66.6 Gy (median 66.6 Gy) with a single fraction of 1.8-2 Gy. Regarding chemotherapy, cisplatin (80 mg/m 2 on day 1) and 5-fluorouracil (800 mg/m 2 on days 2-6) were used concurrently with radiotherapy, every 3-4 weeks for a total of 1-2 courses. Tissue samples from esophageal carcinoma were obtained from the 25 patients by biopsy prior to concurrent CRT, and a semiquantitative analysis of GLUT-1 expression was performed using immunohistochemical staining. High GLUT-1 expression was observed in 7 of 25 (28%) patients, and GLUT-1 expression was significantly correlated with clinical T stage (p=0.0454), clinical N stage (p=0.0324) and initial response to CRT (p=0.0185). Patients with a high GLUT-1 expression had significantly poorer local control (LC) (5-year LC 28.6%) than those with a low expression (5-year LC 73.4%, p<005). Multivariate analysis revealed that GLUT-1 and the number of chemotherapy courses were independent prognostic factors for LC. Patients with a high GLUT-1 expression had significantly lower recurrence-free survival (RFS) compared to those with a low GLUT-1 expression (p=0.0405). Multivariate analysis revealed that GLUT-1, the number of chemotherapy courses and clinical M stage were independent prognostic factors for RFS. GLUT-1 expression was significantly correlated with clinical T stage, clinical N stage and initial response to concurrent CRT, and was predictive of LC and RFS for patients with esophageal cancer treated with concurrent CRT.

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“…5 These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. 4 GLUT1 is ubiquitously expressed and its overexpression has been studied in primary tumors of many tissues including lung, 6,7 breast, 8,9 colon, 10,11 and stomach. 12,13 Even though most studies show an increase in Class I (GLUT1-4) glucose transport facilitators in tumor tissues, some studies suggest that these transporters are not significantly increased in some primary tumors.…”

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confidence: 99%

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma

et al. 2006

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Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n ¼ 38 benign, n ¼ 27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (Po0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (Po0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.

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Differential Expression of Facilitative Glucose Transporter (GLUT) Genes in Primary Lung Cancers and Their Liver Metastases

Cited by 82 publications

References 25 publications

SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions

SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions

Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma

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