GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma

Abstract

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.

Glucose transporter expression in eutopic endometrial tissue and ectopic endometriotic lesions

“…SLC2A5, although significantly higher in ectopic tissue, still showed a very low expression and thus was not considered for further investigation. By contrast, SLC2A1 surprisingly showed no significant change in expression event although it is significantly increased by the hypoxic environment created during malignant lesion growth (Goldman et al 2006, Szablewski 2013.…”

Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

“…Glucose transporter (GLUT) 1, 4, and 8 expression is upregulated in endometrial cancer cells, and may be linked to tumor progression and differentiation (Goldman et al 2006, Shibata et al 2007. Previous, smaller, prospective (Furberg & Thune 2003), and case-control (Levran et al 1984, Rutanen et al 1993 studies have also observed increased risks associated with high glucose levels.…”

“…High glucose levels could increase risk by acting as an energy source for the proliferation of tumor cells (Goldman et al 2006), generating free radicals, or causing oxidative damage to DNA and DNA repair enzymes (Sun 1990, Dandona et al 1996. Glucose transporter (GLUT) 1, 4, and 8 expression is upregulated in endometrial cancer cells, and may be linked to tumor progression and differentiation (Goldman et al 2006, Shibata et al 2007.…”

Regulation of Facilitative Glucose Transporters and AKT/MAPK/PRKAA Signaling via Estradiol and Progesterone in the Mouse Uterine Epithelium1

“…Recent findings show that only SLC2A1 and SLC2A3 are expressed in human endometrium and are increased at secretory phase and in decidua [29]. Another study [30] shows that SLC2A1 and SLC2A8 are expressed in human endometrium and in endometrial cancer. In addition, SLC2A1, SLC2A3, and SLC2A4 are expressed in the rat uterus and are highly increased in the decidual cells of IS [15,31].…”