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 role of thrombospondin (TSP) in tumor angiogenesis and progression remains controversial. The expression of TSP-1 and TSP-2 mRNAs was assessed. Furthermore, TSP association with clinicopathological features, including microvessel count, regarding prognostic significance was examined. Expression of TSP-1 and TSP-2 were assessed by reverse transcriptase-polymerase chain reaction in 18 normal endometrium and 55 endometrial cancer samples. Microvessel counts were determined by immunostaining for factor VIII-related antigen in endometrial cancer specimens. TSP-1 expression of secretory phase endometrium was markedly higher than that of proliferative phase endometrium (p=0.047). Expression of TSP-1 and TSP-2 was detected in 33 (60.0%) and 15 cases (27.3%), respectively, of 55 endometrial cancer samples. TSP-1 expression was significantly higher in tumors recovered from elderly women (p=0.009). TSP-2 expression was significantly higher in malignancies exhibiting cervical and lymph-vascular space involvement (p=0.029 and p=0.009, respectively). Although not statistically significant, microvessel counts were higher in cases displaying increased TSP-1 expression. The microvessel count in patients with TSP-2 expression was markedly higher than that observed in patients lacking TSP-2 expression (p=0.026). Subjects demonstrating TSP-2 mRNA expression displayed significantly poorer prognosis than those lacking TSP-2 mRNA expression (p=0.016). There was no association between TSP-1 mRNA expression and patient outcome. Our findings provide evidence that elevated TSP expression may be associated with an angiogenic phenotype in endometrial cancer. In addition, TSP-2 expression is a marker for poor prognosis in this disease.
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PMID:Thrombospondin-1 and -2 messenger RNA expression in normal and neoplastic endometrial tissues: correlation with angiogenesis and prognosis. 1144 43

Cytochrome P450 1B1 (CYP1B1) catalyzes estrogen hydroxylation and activation of potential carcinogens. Here we explored the role of CYP1B1 in endometrial carcinogenesis. Immunohistochemical staining of endometrial carcinomas showed that CYP1B1 is up-regulated in endometrial cancers. To understand the functional significance of CYP1B1 up-regulation in endometrial cancers with regard to tumorigenesis, we used small interfering RNA-mediated approach to knockdown CYP1B1 in endometrial carcinoma cell line followed by functional assays. Further, to understand the molecular basis of the role of CYP1B1 in endometrial carcinomas, we profiled the expression of key pathway-specific genes and identified several components of cell cycle, apoptosis, and cell adhesion pathways that are potentially regulated by CYP1B1. CYP1B1 depletion in endometrial carcinoma cells leads to decreased cellular proliferation and induces G(0)-G(1) cell cycle arrest. Significantly, CYP1B1 knockdown leads to down-regulated expression of cyclin E1, S-phase kinase-associated protein 2 (SKP2), minichromosome maintenance complex component 4 (MCM4), and RAD51 and up-regulation of p27(Kip1). Also, we identified cyclin E-binding protein (CEBP1) as a novel CYP1B1 target. Attenuation of CYP1B1 expression in endometrial carcinoma cells induces apoptosis and increases expression of IFN-beta (IFNbeta), granzyme A (GRZA), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Importantly, CYP1B1 depletion decreased the invasive potential of the endometrial cancer cells and expression of melanoma cell adhesion molecule (MCAM). In conclusion, our data suggest that CYP1B1 up-regulation plays a crucial role in endometrial carcinogenesis by targeting multiple pathways. We speculate that CYP1B1 inhibition in endometrial carcinomas could be a useful therapeutic approach as it regulates several potential anticancer targets like cyclin E1, Skp2, and TRAIL.
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PMID:Functional significance of cytochrome P450 1B1 in endometrial carcinogenesis. 1969 Jan 33