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)

The BDII rat is genetically predisposed to estrogen-dependent endometrial adenocarcinoma and represents a valuable model for this type of tumor. Tumors arising in strain crosses involving the BDII rats had previously been screened for DNA copy number changes using comparative genome hybridization (CGH). It was found that extra copies of the proximal region of rat chromosome (RNO) 6 commonly could be detected in these tumors. Based on RH-mapping data and comparative mapping with mouse and human, seven cancer-related genes were predicted to be situated in RNO6q14-q16. Rat PACs were isolated for the N-myc proto-oncogene (Mycn), apolipoprotein B (Apob), the DEAD box gene 1 (Ddx1), ornithine decarboxylase 1 (Odc1), proopiomelanocortin (Pomc1), ribonucleotide reductase, M2 polypeptide (Rrm2), and syndecan 1 (Sdc1). The localization of the genes to the region was verified by FISH (fluorescence in situ hybridization) mapping, and the detailed order among them was determined by dual-color FISH. By Southern blot analysis, it was found that the Mycn locus was highly amplified in two out of 10 cell cultures derived from the tumors. In one of them (designated RUT30), the amplification level of Mycn was estimated at 140x. Two other genes were coamplified (Ddx1 and Rrm2) at much lower levels. Similarly, in another culture (designated RUT2), Mycn was amplified more than 40x, whereas three of the other genes (Ddx1, Rrm2, and Odc1) were coamplified at lower levels. Using FISH on metaphase chromosomes from the cell cultures analyzed, the amplified sequences were shown to be located in typical HSRs. With competitive RT-PCR, distinct overexpression of Mycn and Ddx1 could be demonstrated in both RUT2 and RUT30. In addition, Mycn was overexpressed in two other tumors not exhibiting Mycn amplification. Taken together, our results suggest that overexpression of Mycn plays an important role in the development of endometrial cancer in the BDII rat. In humans, Mycn amplification has been reported mainly from tumors of neuronal origin. To our knowledge, this is the first report of Mycn amplification and overexpression in hormone-dependent tumors.
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PMID:Amplification of Mycn, Ddx1, Rrm2, and Odc1 in rat uterine endometrial carcinomas. 1143 25

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.
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PMID:A perspective on the hormonal abnormalities of obesity: are they cause or effect? 1635 9

The MLH3 gene is one of the five mismatch repair (MMR) genes associated with hereditary nonpolyposis colorectal cancer (HNPCC). Eighteen different inherited MLH3 mutations have been reported as pathogenic in an international mutation database. In several cases, a mutation was found in a patient without a family history suggestive of inherited cancer susceptibility. In some cases, a similar mutation was also found in sporadic patients and/or healthy controls. Four patients carried an MLH3 mutation together with another inherited MMR gene variation. No functional analyses have been performed to assess the pathogenicity of these 18 mutations. MLH3 has been assumed to be less important in MMR than the other HNPCC susceptibility genes MSH2, MSH6, MLH1, and PMS2, and accordingly a low-risk gene for colorectal cancer (CRC). To assess the significance of the inherited sequence variations in MLH3, we functionally characterized seven missense mutations (Q24E, R647C, S817G, G933C, W1276R, A1394T, E1451K) scattered throughout the MLH3 polypeptide. The mutations were found in CRC or endometrial cancer patients and reported as pathogenic. Our study showed that the seven mutated MLH3 proteins, in complex with their counterpart MLH1 (MutLgamma), repaired mismatches as the wild type MutLgamma but worse than a heterodimer of MLH1 and PMS2 (MutLalpha). The results confirm that MutLgamma is a less efficient MMR complex than MutLalpha and show that the MLH3 mutations alone do not interfere with MMR. Further studies are needed to evaluate the pathogenicity of MLH3 mutations in compound with other MMR mutations.
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PMID:The first functional study of MLH3 mutations found in cancer patients. 1852 50

Paclitaxel and carboplatin (TC) chemotherapy is an effective and well-tolerated regimen against advanced endometrial cancer. Organic anion transporting polypeptide 1B3 (OATP1B3) and copper transporter 1 (CTR1) are critical for the uptake of paclitaxel and carboplatin, respectively. This study aimed to address the prognostic impact of OATP1B3 and CTR1 in endometrial cancer patients treated with adjuvant TC chemotherapy. We immunohistochemically evaluated the expressions of OATP1B3 and CTR1 in 47 stage III endometrial cancers. The high expression levels of OATP1B3 were significantly correlated with type I tumor (P = 0.0005). In univariate analysis, high expression levels of OATP1B3 (P = 0.047) and CTR1 (P = 0.009) were significantly associated with longer disease-free survival (DFS) and longer overall survival (OS), respectively. The patients with tumors showing high expression levels of at least one of OATP1B3 and CTR1 had potentially longer DFS (P = 0.058) and significantly longer OS (P = 0.003) sin the univariate analysis. Combined OATP1B3/CTR1 expression was the sole independent prognostic factor for longer OS in the multivariate analysis (P = 0.013). Our findings suggest that combined OATP1B3/CTR1 expression is a possible predictive/prognostic factor for a good outcome in stage III endometrial cancer patients treated with adjuvant TC chemotherapy.
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PMID:Prognostic value of organic anion transporting polypeptide 1B3 and copper transporter 1 expression in endometrial cancer patients treated with paclitaxel and carboplatin. 2378 48

O-glycosylation in the field of carcinogenesis has been a critical topic of concern for several decades. The abnormal function of enzymes catalyzing the first step of this process, named polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) has been determined to play an important role in cancer development and metastasis. Accordingly, we investigated the expression of GalNAc-T6 in endometrial carcinoma and evaluated the relationship between invasion characteristics and the cellular level of GalNAc-T6. The results suggested that positive GalNAc-T6 expression is significantly associated with histological grade of tumors and myometrial invasion characteristic. In vitro experiments showed that the over expression of GalNAc-T6 had strong association with the decrease of endometrial cell invasiveness. Taken together, our data support the use of GalNAc-T6 as a potential indicator of good prognosis and noninvasive tumor in patients with endometrial carcinoma.
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PMID:GalNAc-T6 in the relationship with invasion ability of endometrial carcinomas and prognostic significance. 2856 66


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