scholarly journals Cyclin-dependent kinase 5 (CDK5); phosphoinositide 3-kinase (PIK3; PI3K); solute carrier family 2 (facilitated glucose transporter) member 4 (SLC2A4; GLUT4)

2009 ◽  
Vol 2 (9) ◽  
pp. 358-358
Keyword(s):  
Glucose Transporter ◽  
Cyclin Dependent Kinase ◽  
Solute Carrier Family ◽  
Solute Carrier ◽  
Phosphoinositide 3 Kinase ◽  
Cyclin Dependent Kinase 5

scholarly journals SLC36A1-mTORC1 signaling drives acquired resistance to CDK4/6 inhibitors

2019 ◽  
Vol 5 (9) ◽  
pp. eaax6352 ◽  
Author(s):  
Akihiro Yoshida ◽  
Yiwen Bu ◽  
Shuo Qie ◽  
John Wrangle ◽  
E. Ramsay Camp ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Fragile X ◽  
Acquired Resistance ◽  
Mammalian Target Of Rapamycin ◽  
Cyclin Dependent Kinase ◽  
Solute Carrier Family ◽  
Potential Therapeutic Target ◽  
Mtorc1 Signaling ◽  
Solute Carrier

The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X mental retardation syndrome–associated protein 1 overexpression, which promotes SLC36A1 translation and subsequently mTORC1. Last, we demonstrate that a combination of a CDK4/6 inhibitor with an mTORC1 inhibitor has increased therapeutic efficacy in vivo, providing an important avenue for improved therapeutic intervention in aggressive melanoma.

scholarly journals Assignment of solute carrier family 2 (facilitated glucose transporter), members <i>SLC2A2</i>, <i>SLC2A3</i>, <i>SLC2A5</i>, <i>SLC2A8</i> and <i>SLC2A12</i> to porcine chromosomes by somatic cell and radiation hybrid panel mapping (Brief report)

2007 ◽  
Vol 50 (1) ◽  
pp. 114-115
Author(s):  
K. Liu ◽  
S. Zhao ◽  
B. Liu ◽  
B. Fan ◽  
C. Li ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Radiation Hybrid ◽  
Mammalian Cells ◽  
Somatic Cell Hybrid ◽  
Glucose Transporter ◽  
Radiation Hybrid Panel ◽  
Somatic Cell Hybrid Panel ◽  
Solute Carrier Family ◽  
Hydrophilic Character ◽  
Solute Carrier

Abstract. The transport of glucose plays an important role in cellular glucose homeostasis and metabolism [1]. Due to the hydrophilic character of glucose, the transport of glucose in and out of cells requires specific carrier proteins. The mammalian facilitative glucose transport family, which contains the energy-independent transporters (gene symbol SLC2A, protein symbol GLUT), catalyzes the entry of glucose into mammalian cells by facilitative diffusion down a concentration gradient. Thirteen members of mammalian GLUT family have been now characterized [1]. In swine, the chromosomal locations for the five genes (SLC2A2, SLC2A3, SLC2A5, SLC2A8 and SLC2A12) have not yet been determined. In this study, as the first step to better understand of the roles of these GLUTs in pigs which could subsequently be beneficial for pig production, we report the mapping of the five genes using both porcine somatic cell hybrid panel (INRA-SCHP) and radiation hybrid panel (IMpRH).

scholarly journals Insulin regulation of solute carrier family 2 member 1 (glucose transporter 1) expression and glucose uptake in decidualizing human endometrial stromal cells: an in vitro study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ivika Jakson ◽  
Dorina Ujvari ◽  
Sebastian Brusell Gidlöf ◽  
Angelica Lindén Hirschberg
Keyword(s):  
Glucose Uptake ◽  
Stromal Cells ◽  
Glucose Transporter ◽  
Mrna Levels ◽  
Solute Carrier Family ◽  
Endometrial Stromal Cells ◽  
Glucose Transporter 1 ◽  
Protein Levels ◽  
Solute Carrier

Abstract Background Solute carrier family 2 member 1 (SLC2A1; previously known as glucose transporter 1), is the most abundant glucose transporter in human endometrium and is up-regulated during decidualization, whereas high insulin may have a negative impact on this process. The present study aimed to investigate the effect of insulin on the expression of SLC2A1 and glucose uptake in decidualizing human endometrial stromal cells. Methods We induced in vitro decidualization of endometrial stromal cells obtained from regularly menstruating healthy non-obese women. The cells were treated with increasing concentrations of insulin, and the involvement of the transcription factor forkhead box O1 (FOXO1) was evaluated using a FOXO1 inhibitor. SLC2A1 mRNA levels were measured by Real-Time PCR and protein levels were evaluated by immunocytochemistry. Glucose uptake was estimated by an assay quantifying the cellular uptake of radioactive glucose. One-way ANOVA, Dunnett’s multiple comparisons test and paired t-test were used to determine the statistical significance of the results. Results We found that insulin dose-dependently decreased SLC2A1 mRNA levels and decreased protein levels of SLC2A1 in decidualizing human endometrial stromal cells. Transcriptional inactivation of FOXO1 seems to explain at least partly the down-regulation of SLC2A1 by insulin. Glucose uptake increased upon decidualization, whereas insulin treatment resulted in a slight inhibition of the glucose uptake, although not significant for all insulin concentrations. Conclusions These results indicate an impairment of decidualization by high concentrations of insulin. Future studies will determine the clinical significance of our results for endometrial function and decidualization in women with insulin resistance and hyperinsulinemia.

Diet-induced epigenetic regulation in vivo of the intestinal fructose transporter Glut5 during development of rat small intestine

2011 ◽  
Vol 435 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Takuji Suzuki ◽  
Veronique Douard ◽  
Kazuki Mochizuki ◽  
Toshinao Goda ◽  
Ronaldo P. Ferraris
Keyword(s):  
Rna Polymerase Ii ◽  
Glucose Transporter ◽  
Histone H3 ◽  
Solute Carrier Family ◽  
Metabolic Complications ◽  
Pol Ii ◽  
Histone H4 Acetylation ◽  
Histone H3 Acetylation ◽  
Solute Carrier ◽  
H3 Acetylation

Metabolic complications arising from excessive fructose consumption are increasing dramatically even in young children, but little is known about ontogenetic mechanisms regulating Glut5 [glucose transporter 5; encoded by the Slc2a5 (solute carrier family 2 member 5) gene]. Glut5 expression is low postnatally and does not increase, unless luminal fructose and systemic glucocorticoids are present, until ≥14 days of age, suggesting substrate-inducible age- and hormone-sensitive regulation. In the present study, we perfused intestines of 10- and 20-day-old rats with either fructose or glucose then analysed the binding of Pol II (RNA polymerase II) and GR (glucocorticoid receptor), as well as acetylation of histones H3 and H4 by chromatin immunoprecipitation. Abundance of Glut5 mRNA increased only with fructose perfusion and age, a pattern that matched that of Pol II binding and histone H3 acetylation to the Glut5 promoter. Although many regions of the Glut5 promoter respond to developmental signals, fewer regions perceive dietary signals. Age- but not fructose-dependent expression of Sglt1 [sodium-dependent glucose co-transporter 1 encoded by the Slc5a1(solute carrier family 5 member 1) gene] also correlated with Pol II binding and histone H3 acetylation. In contrast, G6Pase (glucose-6-phosphatase; encoded by the G6pc gene) expression, which decreases with age and increases with fructose, is associated only with age-dependent changes in histone H4 acetylation. Induction of Glut5 during ontogenetic development appears to be specifically mediated by GR translocation to the nucleus and subsequent binding to the Glut5 promoter, whereas the glucocorticoid-independent regulation of Sglt1 by age was not associated with any GR binding to the Sglt1 promoter.

Sign in / Sign up

Export Citation Format

Share Document