LINC00346 regulates glycolysis by modulation of glucose transporter 1 in breast cancer cells

Abstract Background Current treatment methods for patients with triple-negative breast cancer (TNBC) are very limited, and the prognosis of TNBC is relatively poor. It has been reported that glucose transporter 1 (GLUT1) is overexpressed in breast cancer cells; however, its association with the prognosis is mostly unclear. Moreover, retinoblastoma gene 1 (RB1) might be used as a biomarker for the sensitivity of breast cancer cells to GLUT1 inhibitors, which brought us to the hypothesis that there might be a close correlation between the expression of GLUT1–4 and the expression of RB1. Methods In this study, we systematically analyzed the co-expression of GLUT1–4 and the influence of GLUT1–4 gene expression on the prognosis of breast cancer using data mining methods. We also explored possible relationships between GLUT1–4 and RB1 expression in breast cancer tissues. We used public databases such as ONCOMINE, GEPIA, LinkedOmics, and COEXPEDIA. Results According to the results, the mRNA expression of SLC2A1 was significantly higher in breast cancer, while the expression levels of SLC2A2–4 were downregulated. The results also indicate that GLUT1 expression does not have significant influence on the overall survival of patients with breast cancer. The mRNA expression of SLC2A1 and RB1 is significantly correlated, which means that tissues with high RB1 mRNA expression might have relatively higher mRNA expression of SLC2A1; however, further study analyzing their roles in the expression regulation pathways with human samples is needed to verify the hypothesis. Conclusions The mRNA expression of SLC2A1 was significantly higher in breast cancer. The overall survival of breast cancer patients wasn’t significantly correlated with GLUT1–4 expression. The mRNA expression of SLC2A1 and RB1 is significantly correlated according to the analysis conducted in LinkedOmics. It provides reference for future possible individualized treatment of TNBC using GLUT1 inhibitors, especially in patients with higher mRNA expression of RB1. Further study analyzing the roles of these two genes in the regulation pathways is needed.

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Estrogen and Progesterone Up-Regulate Glucose Transporter Expression in ZR-75-1 Human Breast Cancer Cells

Endocrinology ◽

10.1210/en.2003-0294 ◽

2003 ◽

Vol 144 (10) ◽

pp. 4527-4535 ◽

Cited By ~ 27

Author(s):

Rodolfo A. Medina ◽

Ana Maria Meneses ◽

Juan Carlos Vera ◽

Catherine Guzman ◽

Francisco Nualart ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Glucose Transporter ◽

Combined Therapy ◽

Hormone Replacement ◽

Breast Cancer Incidence ◽

Hormonal Treatment ◽

Glut1 Expression ◽

17Β Estradiol

Breast cancer incidence increases in women receiving combined estrogen and progesterone therapy. Breast tumors show increased expression of the glucose transporter GLUT1. We determined the effect of these hormones on GLUT1–4 expression and deoxyglucose transport in ZR-75-1 breast cancer cells. Immunoblotting, immunocytochemistry, flow cytometry, and RT-PCR showed that GLUT1 expression is up-regulated by progesterone and, to a greater degree, combined therapy. GLUT2 expression is unaffected by hormonal treatment. GLUT3 protein and RNA is up-regulated by progesterone and combined therapy, and GLUT4 protein expression is up-regulated by all hormonal treatments. Deoxyglucose transport studies revealed the presence of three transport components with characteristics corresponding to GLUT1/4, GLUT2, and GLUT3. 17β-Estradiol produced a slight increase in transport at the Michaelis constant (Km) corresponding to GLUT3. Progesterone produced a small increase in transport at the Km corresponding to GLUT1/4, and combined 17β-estradiol and progesterone produced a small increase in transport at the Km corresponding to GLUT3 and a large increase in transport at the Km corresponding to GLUT1/4. This indicates that 17β-estradiol and progesterone differentially regulate GLUT1–4 expression and that these changes correlate to changes in glucose uptake. We postulate that combined hormone replacement therapy provides a survival advantage to developing ZR-75 breast cancer cells.

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Glucose Transporter 3 Is Essential for the Survival of Breast Cancer Cells in the Brain

Cells ◽

10.3390/cells8121568 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1568 ◽

Cited By ~ 1

Author(s):

Min-Hsun Kuo ◽

Wen-Wei Chang ◽

Bi-Wen Yeh ◽

Yeh-Shiu Chu ◽

Yueh-Chun Lee ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Metabolism ◽

Brain Metastasis ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Glucose Transporter ◽

Metastatic Breast ◽

Breast Cancer Brain Metastasis ◽

The Brain

Breast cancer brain metastasis commonly occurs in one-fourth of breast cancer patients and is associated with poor prognosis. Abnormal glucose metabolism is found to promote cancer metastasis. Moreover, the tumor microenvironment is crucial and plays an active role in the metabolic adaptations and survival of cancer cells. Glucose transporters are overexpressed in cancer cells to increase glucose uptake. The glucose transporter 3 (GLUT3) is a high-affinity glucose transporter that is highly expressed in mammalian neurons. GLUT3 is also overexpressed in several malignant brain tumors. However, the role of GLUT3 in breast cancer brain metastasis remains unknown. The results of the present study demonstrated that GLUT3 is highly overexpressed in brain metastatic breast cancers and mediates glucose metabolic reprogramming. Furthermore, knockdown of cAMP-response element binding protein (CREB) could directly regulate GLUT3 expression in brain metastatic breast cancer cells. Notably, we verified and provided a novel role of GLUT3 in mediating glucose metabolism and assisting breast cancer cells to survive in the brain to promote brain metastasis.

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Combination of glucose transporter inhibitors and oestrone analogues on breast cancer cells

Suid-Afrikaanse Tydskrif vir Natuurwetenskap en Tegnologie ◽

10.4102/satnt.v33i1.1263 ◽

2014 ◽

Vol 33 (1) ◽

Author(s):

A. Van Tonder ◽

A.J. Joubert ◽

A.D. Cromarty

Keyword(s):

Breast Cancer ◽

Combination Therapy ◽

Cancer Cells ◽

Clinical Setting ◽

Breast Cancer Cells ◽

Glucose Transporter ◽

Molecular Subtypes ◽

Chemotherapeutic Agents ◽

Reduced Toxicity ◽

Synergistic Combinations

Combinations of chemotherapeutic agents are commonly used in the clinical setting as this allows for a reduction in the dose of each agent, and thus reduced toxicity, with increased therapeutic efficacy. This study proved the feasibility of synergy between two novel oestrone analogues and GLUT inhibitors. The synergistic combinations which have been identified indicate that the different molecular subtypes of breast cancer, as represented by the cell lines used, respond differently to the combination therapy. These differences will be further investigated.

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