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)

The adult human endometrium rapidly cycles through stages of cell proliferation, differentiation and degeneration. Inappropriate endometrial cell differentiation is a contributing factor in diseases such as endometrial carcinoma and endometriosis. We have identified two homeobox genes that may play a role in the control of endometrial cell differentiation and development. In-situ mRNA hybridization experiments were used to show differential expression of DLX4 at different phases of the endometrial cycle. Higher levels of DLX4 expression were observed in proliferative phase endometrial epithelium compared with secretory phase endometrial epithelium. The HB24 homeobox gene was shown to be expressed in both the proliferative and secretory phase endometrial epithelium. We predict that DLX4 and HB24 will be required for the transcriptional control of genes important for endometrial cell differentiation. Furthermore, we propose that DLX4 and HB24 are part of a conserved combinatorial code of homeobox genes that are required for controlling epithelial-mesenchymal cell interactions in the endometrium.
 ...
PMID:Homeobox genes DLX4 and HB24 are expressed in regions of epithelial-mesenchymal cell interaction in the adult human endometrium. 966 37

Homeobox genes encode transcription factors that control cell differentiation and play essential roles in developmental patterning. Increasing evidence indicates that many homeobox genes are aberrantly expressed in cancers, and that their deregulation significantly contributes to tumor progression. The homeobox gene HOXA10 controls uterine organogenesis during embryonic development and functional endometrial differentiation in the adult. We investigated whether HOXA10 expression is deregulated in endometrial carcinomas, and how counteracting this aberrant expression modifies tumor behavior. We found that down-regulation of HOXA10 expression in endometrial carcinomas strongly correlates with increased tumor grade and is associated with methylation of the HOXA10 promoter. Enforced expression of HOXA10 in endometrial carcinoma cells inhibited invasive behavior in vitro and tumor dissemination in nude mice. The inhibitory effect of HOXA10 on invasive behavior was attributable at least in part to the ability of HOXA10 to induce expression of the epithelial cell adhesion molecule E-cadherin by down-regulating expression of Snail, a repressor of E-cadherin gene transcription. These findings reveal a novel role for HOXA10 deregulation in the progression of endometrial carcinoma by promoting epithelial-mesenchymal transition.
 ...
PMID:Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: role in epithelial-mesenchymal transition. 1642 22

It is well established that there is a dynamic relationship between the expanding tumor and the host surrounding tissue. Cancer-associated fibroblasts (CAFs), the most common cellular population found in the tumor microenvironment, supporting tumor growth and dissemination. Here, we set out to determine the factors that may be involved in dramatic alteration of gene expression pattern in CAFs, focusing on microRNA and transcriptional regulators. We established matched pairs of human CAFs isolated from endometrial cancer and normal endometrial fibroblasts. MicroRNA and mRNA analyses identified differential expression of 11 microRNAs, with miR-31 being the most downregulated microRNA in CAFs (p = 0.007). We examined several putative miR-31 target genes identified by microarray analysis and demonstrated that miR-31 directly targets the homeobox gene SATB2, which is responsible for chromatin remodeling and regulation of gene expression, and was significantly elevated in CAFs. The functional relevance of miR-31 and SATB2 were tested in in vitro models of endometrial cancer. Overexpression of miR-31 significantly impaired the ability of CAFs to stimulate tumor cell migration and invasion, without affecting tumor cell proliferation. Genetic manipulation of SATB2 levels in normal fibroblasts or CAFs showed that, reciprocally to miR-31, SATB2 increased tumor cell migration and invasion, while knockdown of endogenous SATB2 in CAFs reversed this phenotype. Introduction of SATB2 into normal fibroblasts stimulated expression of a number of genes involved in cell invasion, migration and scattering. These findings provide new insights into tumor-stroma interaction and document that miR-31 and its target gene SATB2, are involved in regulation of tumor cell motility.
 ...
PMID:The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. 2126 Sep 45

Homeobox genes encode a group of transcription factors that regulate embryonic development, organ differentiation and cell proliferation. Some researchers found that homeobox gene family could regulate the expression of cell cycle-related factors which are involved in tumorigenesis. The aim of the present study was to determine whether HOXA10 gene could regulate the expression of p21 and control the cell cycle in endometrial cancer. Real-time PCR and Western blot were used to analyze HOXA10 and p21 gene expression in tissue samples of normal endometrium and endometrial cancer. Upregulate and downregulate HOXA10 gene in endometrial cancer cells by HOXA10-vector and HOXA10-siRNA, p21 mRNA and protein expression were tested by real-time PCR and Western blot. FCM analyze the cell cycle alteration, and cell count and EdU assay were recruited to detect cell proliferative activity after upregulation of HOXA10. Expression of HOXA10 and p21 gene decreased in endometrial cancer, and the expression level of HOXA10 was correlated with cancer grade. The percentage of G1 phase cells increased, and cell proliferative activity decreased after upregulate HOXA10 expression. The expression of p16, p27, Myc, Cyclin D1, Cyclin E, CDK2, CDK4 and CDK6 did not alter after upregulation HOXA10. P21 gene mRNA and protein increased/decreased after upregulation/downregulation HOXA10 expression in cancer cells. HOXA10 regulates G1 phase arrest in endometrial cancer which may be mediated by p21.
...
PMID:Upregulation HOXA10 homeobox gene in endometrial cancer: role in cell cycle regulation. 2494 91

The expression of homeobox gene DLX4 has been verified in some tumors, but not in endometrial cancer. We found that expression of DLX7, a splicing isoform of DLX4, did not show any significant difference in expression between endometrial cancer and endometrium. However, BP1, another splicing isoform of DLX4, was highly expressed in endometrial cancer, and its expression was positively correlated with patient prognosis, cancer pathological grade, tumor invasion and metastasis. Lentiviral-mediated expression of BP1 in HEC-1-B cells accelerated the cell cycle progression from G0/G1 into S phase, and promoted cell proliferation and migration both in vitro and in vivo. Real-time PCR and western blotting showed that the expression levels of p15, p21 and E-cadherin significantly decreased, and levels of cyclinD1 and MMP-2 increased in endometrial cancer cells. In conclusion, our results demonstrate that high expression of BP1 is associated with poor prognosis in patients with endometrial cancer and promotes cell proliferation and migration.
 ...
PMID:Overexpression of BP1, an isoform of Homeobox Gene DLX4, promotes cell proliferation, migration and predicts poor prognosis in endometrial cancer. 3110 Mar 38