Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

JAZF1 is a novel gene that is associated with diabetes mellitus and prostate cancer according to genomewide association studies; however, little is known about the function of this gene in regulating metabolism. In the present study, we have shown the expression of JAZF1 in various mouse tissues. To elucidate its role in metabolism, we investigated the influence of an overexpression of JAZF1 on 3T3-L1 adipose cells and hepatoma carcinoma Hepa1-6 cells that represent target tissues for diabetes and insulin resistance. In both cells, JAZF1 overexpression led to a substantial reduction in the expression of acetyl-coenzyme A carboxylase, fatty acid synthetase, and sterol regulatory element-binding protein 1 messenger RNA (mRNA). The level of hormone-sensitive lipase mRNA significantly increased. The expression of JAZF1 in 3T3-L1 adipocyte exhibited suppressive effects on lipid accumulation and decreased droplet size. In addition, the transcription for glucose transport 1 was significantly higher than the control in the Hepa1-6 cell line; but it was not significantly different in 3T3-L1. These results showed that JAZF1 in adipocytes and liver cells reduces lipid synthesis and increases lipolysis mainly by down-regulating the levels of sterol regulatory element-binding protein 1, acetyl-coenzyme A carboxylase, and fatty acid synthetase mRNA expression and by increasing hormone-sensitive lipase mRNA expression. Because it had an effect on the decrease of the maturation of lipid droplets and fat storage, we speculate that JAZF1 might represent a potential target against diabetes and obesity.
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PMID:The role of JAZF1 on lipid metabolism and related genes in vitro. 2058 Mar 84

Despite currently available therapies, most patients diagnosed with acute myeloid leukemia (AML) die of their disease. Tumor-host interactions are critical for the survival and proliferation of cancer cells; accordingly, we hypothesize that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Because adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukemia cell interactions to determine if they are essential for the growth and survival of AML. Using in vivo and in vitro models of AML, we show that bone marrow adipocytes from the tumor microenvironment support the survival and proliferation of malignant cells from patients with AML. We show that AML blasts alter metabolic processes in adipocytes to induce phosphorylation of hormone-sensitive lipase and consequently activate lipolysis, which then enables the transfer of fatty acids from adipocytes to AML blasts. In addition, we report that fatty acid binding protein-4 (FABP4) messenger RNA is upregulated in adipocytes and AML when in coculture. FABP4 inhibition using FABP4 short hairpin RNA knockdown or a small molecule inhibitor prevents AML proliferation on adipocytes. Moreover, knockdown of FABP4 increases survival in Hoxa9/Meis1-driven AML model. Finally, knockdown of carnitine palmitoyltransferase IA in an AML patient-derived xenograft model improves survival. Here, we report the first description of AML programming bone marrow adipocytes to generate a protumoral microenvironment.
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PMID:Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. 2828 44