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

PRKCDBP is a putative tumor suppressor located at 11p15.4, where frequent genomic loss has been observed in human cancers. We explored the possible association between an intra-exonic single nucleotide polymorphism (SNP), rs1051992, that results in a Leu to Pro substitution, and risk for endometrial carcinogenesis. We assessed the genotype of rs1051992 in endometrial cancer tissues from 147 patients and normal endometrial tissue from 191 healthy individuals by restriction endonuclease PvuII-based genotyping. Allele frequencies in the cancer specimens were compared with those in the healthy controls. We also evaluated the association between polymorphisms at this locus and histopathological features of endometrial cancer.
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PMID:Genetic polymorphism of PRKCDBP is associated with an increased risk of endometrial cancer. 2302 Jun 6

Endometrial cancer (EC) is one of the most common female malignancies. The patients with high-risk factors may have poor prognosis. Therefore, there is an urgent need to find a new molecule to more accurately predict survival of patients. Leucine-rich-alpha-2-glycoprotein1 (LRG1), one of leucine-rich repeat family, was closely associated with cancer metastasis and poor prognosis. The biological functions and the expression level of LRG1 remain obscure in EC. In this study, by immunohistochemical analysis of 242 EC patient tissues, we found that LRG1 expression was associated with stage and lymphatic metastasis in both test cohort (133 patients) and validation cohort (109 patients). Furthermore, to investigate the prognostic value of LRG1 in endometrial carcinoma, we analyzed the correlation between variables and overall survival with Cox proportional hazard regression. The result showed that LRG1 was an independent prognostic factor for overall survival of endometrial carcinoma patients. To further evaluate the prognostic efficiency of LRG1 in endometrial carcinoma, we compared the sensitivity and specificity of LRG1 in endometrial carcinoma prognosis by logistic regression. The result showed that LRG1 combining with other clinicopathological risk factors was a stronger prognostic model than clinicopathological risk factors alone or their combination. Thus, LRG1 potentially offered clinical value in directing personal treatment for endometrial carcinoma patients.
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PMID:LRG1 is an independent prognostic factor for endometrial carcinoma. 2476 Feb 73

l-type amino acid transporters (LAT1-4) are expressed in various cancer types and are involved in the uptake of essential amino acids such as leucine. Here we investigated the expression of LAT1-4 in endometrial adenocarcinoma and evaluated the contribution of LATs to endometrial cancer cell growth. Analysis of human gene expression data showed that all four LAT family members are expressed in endometrial adenocarcinomas. LAT1 was the most highly expressed, and showed a significant increase in both serous and endometrioid subtypes compared to normal endometrium. Endometrioid patients with the highest LAT1 levels exhibited the lowest disease-free survival. The pan-LAT inhibitor BCH led to a significant decrease in cell growth and spheroid area in four endometrial cancer cell lines tested in vitro. Knockdown of LAT1 by shRNA inhibited cell growth in HEC1A and Ishikawa cells, as well as inhibiting spheroid area in HEC1A cells. These data show that LAT1 plays an important role in regulating the uptake of essential amino acids such as leucine into endometrial cancer cells. Increased ability of BCH compared to LAT1 shRNA at inhibiting Ishikawa spheroid area suggests that other LAT family members may also contribute to cell growth. LAT1 inhibition may offer an effective therapeutic strategy in endometrial cancer patients whose tumours exhibit high LAT1 expression.
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PMID:LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma. 2748 61

Although endometrial cancer is the most common type of gynecological malignancy in developed countries, its molecular etiology is not well understood. Leucine-rich repeat and immunoglobulin-like domain 2 (LRIG2) is an evolutionarily conserved gene, but its functions in the endometrium are unknown. In this study, we found that LRIG2 is highly downregulated in endometrial adenocarcinoma patients and that it functions as a tumor suppressor. LRIG2 induced the mitochondrion-mediated apoptotic pathways by regulating stoichiometric balance among BCL-2 family proteins, whereby pro-survival members, MCL-1 and BCL-xL, were downregulated and pro-apoptotic BAK and BAX were upregulated. LRIG2 also inhibited proliferation of the Hec-1A and Ishikawa endometrial adenocarcinoma cells by upregulating p21. LRIG2 induced BAX- and BAK-dependent cell death that was efficiently prevented by MCL-1 overexpression. Furthermore, we found that LRIG2 unexpectedly phosphor-activates phosphoinositide 3-kinase (PI3K)/AKT and epidermal growth factor receptor (EGFR), which are conventionally accepted as survival signaling cues in diverse types of cancer. We observed that PI3K/AKT and EGFR serve as key kinases that have roles as growth suppressors of Hec-1A endometrial cancer cells by mediating the LRIG2-induced modulation of the BCL-2 family of proteins and p21. In vivo delivery of antisense DNAs against LRIG2 promoted the Hec-1A endometrial tumor growth in a xenograft mouse model, and immunoblotting of these tumor extracts showed consistent modulation of AKT, EGFR, the BCL-2 family members, and p21. Thus, our results demonstrated that LRIG2 is a growth suppressor of endometrial adenocarcinoma cells.
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PMID:LRIG2 is a growth suppressor of Hec-1A and Ishikawa endometrial adenocarcinoma cells by regulating PI3K/AKT- and EGFR-mediated apoptosis and cell-cycle. 2935 88

Branched-chain amino acid aminotransferase 1 (BCAT1) enzyme is an aminotransferase of glutamate and branched-chain amino acids (BCAAs), which is required for survival of various cancers. However, the role of BCAT1 in human endometrial cancer (EC) remains unknown. We analyzed the expression of BCAT1 in endometrial lesions using IHC. After BCAT1 gene knockdown and activity inhibition, cell proliferation, apoptosis, and metabolism were detected using CCK-8 assay, flow cytometry, and LC-MS/MS analysis. We analyzed molecular signature characteristics to understand how BCAT1 promotes cell proliferation. In this study, we demonstrated a significant increase in BCAT1 expression from normal endometrium to atypical endometrial hyperplasia (AEH) and then to EC, and the expression of BCAT1 in EC samples was related to tumor grade, FIGO stage and lymph node metastasis. Next, cell proliferation was markedly inhibited by lentiviral BCAT1 knockdown or Gbp treatment, but this had little effect on apoptosis rate. Further, BCAT1 knockdown resulted in 31.2% and 33.3% decreases in the amount of intracellular isoleucine and leucine produced, respectively, relative to a control. BCAT1 knockdown or activity inhibition resulted in a decrease of pS6K, a downstream target kinase of mTORC1. In conclusion, our study showed that BCAT1 is essential for EC progression and to increase EC cell proliferation through the production of BCAAs to activate the mTORC1 pathway, providing ideas for clinicians to identify metabolism-based targeted approaches for patients with EC.
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PMID:BCAT1 promotes proliferation of endometrial cancer cells through reprogrammed BCAA metabolism. 3194 41


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