Role for glucose transporter 1 protein in human breast cancer

Abstract

Glycolysis is increased in cancer cells compared with normal cells. It has been shown that glucose enters cells via a family of five functional glucose transporters (GLUT). However, GLUT expression appears to be altered in human breast cancer, which may serve as a selective advantage and facilitate the metastatic potential of these cells. The relationship of GLUT isoform expression and breast cancer cell invasiveness has not been adequately addressed. Thus, the purpose of this study was to investigate whether an association exists between GLUT expression and human breast cancer cell invasiveness. Invasiveness of the human breast cancer lines MCF-7, MDA-MB-435 and MDA-MB-231 was measured using an in vitro assay and compared with cellular GLUT isoform expression, assessed by Western blot analysis and verified by immunohistochemistry in a poorly differentiated human ductal breast cancer. Cell surface GLUT-1 expression was associated with the invasive ability of MCF-7 (2.0 + 0.02%), MDA-MB-435 (6.4 +/- 0.4%), and MDA-MB-231 (19.3 +/- 2.0%). However, GLUT-2 and GLUT-5 were inversely associated with invasiveness; GLUT-3 expression was variable; and GLUT-4 was undetected. In a poorly differentiated human ductal breast cancer, in situ GLUT-1 staining was intense. GLUT-1 expression was associated with the in vitro invasive ability of human breast cancer cells which was validated in situ. If this relationship is found to exist in a larger number of human breast cancer tissues, it may be possible to develop diagnostic and therapeutic strategies based on targeted GLUT isoform expression.

Antitumor activity of efrapeptins, alone or in combination with 2-deoxyglucose, in breast cancer in vitro and in vivo

“…These observations are in agreement with the idea that MDA-MB-231 cells rely on aerobic glycolysis to fulfill their energetic demands, while MCF-7 cells utilize OXPHOS (Guppy et al 2002). Here, it should be noted that, while we did not observe Glut-1 expression in MCF-7 cells, other investigators reported that MCF-7 cells did express Glut-1, even though the expression was greatly reduced compared to MDA-MB-231 cells (Grover-McKay et al 1998).…”

Glucose transporter Glut-1 is detectable in peri-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays

“…This has application in the clinic, where hypoxia driven changes in Glut-1 expression relates to the degree of malignant transformation and invasive portential of cervix metaplasia (Rudlowski et al, 2003), breast cancer (Gatenby et al, 2007) and hepatocellular carcinoma (Amann et al, 2009). Glut-1 expression correlates with tumor invasiveness (Grover-McKay et al, 1998) and promotes increased proliferative activity, which is associated with the loss of functional p53 (Schwartzenberg-Bar-Yoseph et al, 2004).…”

Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy

“…GLUT1 is widely considered responsible for glucose transport in breast tissue [117][118][119][120]. Existence of GLUT2 in breast was controversial and no apparent difference was observed between normal and malignant tissues [117,118,121]. GLUT3, which is more likely expressed in the brain, was not detected in either normal or tumor breast tissues [118], except of breast cancer cell line ZR-75 [122].…”

“…GLUT3, which is more likely expressed in the brain, was not detected in either normal or tumor breast tissues [118], except of breast cancer cell line ZR-75 [122]. The expression of GLUT4 was found in various human malignant breast tissues, but not in human breast cancer cell lines -MCF-7, MDA-MB-435 and MDA-MB-23 [117,118,121]. The high-affinity fructose transporter GLUT5 was selectively expressed in human breast cancer tissues, indicating that fructose may be a good energy substrate in tumor cells [116,119].…”

“…Because GLUT1 was exclusively found in human breast cancer biopsies and its expression was strongly associated with tumor grade, proliferation as well as invasiveness [111,120,121], GLUT1 has been proposed to be a new marker for diagnosis and prognosis of human breast cancers, an indication of tumor aggressiveness, and a possible therapeutic target for patients with breast cancer [114,175]. It has been demonstrated that drug mediated inhibition of glucose transport in-creased the effectiveness of several anti-tumor drugs and effectively induced growth arrest and apoptosis in lung, breast cancer and leukemia cell lines [175,176].…”