Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclin D1 regulates G1 progression and is important in the development and proliferation of various human cancers. Cyclin D1 gene expression is activated by the Ras kinase cascade. Nuclear cyclin D1 levels are dependent on cytoplasmic degradation of cyclin D1 via ubiquitin-mediated proteolysis. We sought to determine whether the important MAPK signaling pathway, in the cyclin D1 cascade, including FBXW8, Cullin1, and the ubiquitination pathway mediated these effects. Ursolic acid (UA) treatment of SNG-2 cells, an endometrial cancer cell line, decreased cyclin D1, pERK1/2, FBXW8, and Cullin1 levels in a dose- and time-dependent manner. RING-type E3 ligase consists of CulIin1, Rbx, Skp1, and a member of the F-box protein family. In SNG-2, both dose- and time-dependent inhibition of Rbx 1 were observed following treatment with UA. Moreover, in HEC108 cells, another endometrial cancer cell line, UA treatment decreased cyclin D1, pERK1/2, and Cullin1 levels in a dose- and time-dependent manner and UA markedly inhibited FBXW8. Treatment of HEC108 cells moderately decreased Rbx1 in a dose- and-time-dependent fashion. In contrast, UA treatment increased ubiquitinated proteins in a dose- and time-dependent manner in both cell lines. RING-type E3 ligase accumulated in the cytoplasm following UA treatment of SNG-2cells. That in turn prevented cytoplasmic degradation of cyclin D1 via RING-type E3 (SCF E3s) ligase. In conclusion, our study found inhibition of the MAPK- cyclin D1 pathway and RING type E3 ligase (SCF E3s) in both endometrial cancer cell lines. Furthermore, CD36 was noted as a cell surface receptor for UA.
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PMID:Effect of ursolic acid on MAPK in cyclin D1 signaling and RING-type E3 ligase (SCF E3s) in two endometrial cancer cell lines. 2408 69

F-box and WD repeat domain containing (FBXW) family of E3 ligases has 10 members that ubiquitinate substrate proteins for proteasome-mediated degradation. Publicly archived datasets from The Cancer Genome Atlas (TCGA), Prostate Cancer Transcriptome Atlas (PCTA), and cBioPortal were analyzed for mRNA expression and genetic alterations of 10 FBXW genes. We found that FBXW7 mRNA expression was significantly decreased in primary prostate cancers compared to normal prostate tissues, whereas mRNA expression of FBXW8-10 was significantly increased in primary prostate cancers compared to normal prostate tissues. FBXW7 mRNA expression was also significantly decreased in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and uterine corpus endometrial carcinoma. In contrast, FBXW7 mRNA expression was significantly increased in cholangiocarcinoma, colon adenocarcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pheochromocytoma and paraganglioma, and thyroid carcinoma. Compared to normal tissues, FBXW5 mRNA expression was significantly increased in breast invasive carcinoma, cholangiocarcinoma, kidney chromophobe, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, thyroid carcinoma, and uterine corpus endometrial carcinoma, whereas FBXW5 mRNA expression was only significantly decreased in colon adenocarcinoma. There were not any significant differences in gene copy number gains, losses, or gene simple somatic mutations between primary prostate cancers and normal prostate tissues. The mRNA expression levels of FBXW5, 7, 8, 9, and 12 were significantly higher in metastatic castration-resistant prostate cancers (mCRPCs) than primary prostate cancers, whereas mRNA expression levels of FBXW1 and 4 were significantly lower in mCRPCs than primary prostate cancers. All 10 FBXW genes had significantly more overall gene alterations including gene amplifications in mCRPCs than primary prostate cancers. FBXW5 and 7 had significantly more gene deep deletions in mCRPCs than primary prostate cancers and FBXW7 had significantly more gene missense mutations in mCRPCs than primary prostate cancers. Our findings suggest that different FBXW genes have differential mRNA expression in prostate cancer and other cancer types and their gene amplifications are significantly more in mCRPCs than primary prostate cancers. FBXW7 mRNA expression is consistently decreased in primary prostate cancers compared to normal prostate tissues.
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PMID:Genome and transcriptome profiling of FBXW family in human prostate cancer. 3292 7