Gene expression in endometrial cancer cells treated with metastin-10 (kp10)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Tsukasa Baba
PROVIDER: E-GEOD-25458 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Invasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis, resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, KISS1 (kisspeptin), and its endogenous receptor, GPR54, has been reported in several cancers, but the significance of the KISS1/GPR54 axis in endometrial cancer metastasis has not been clarified. Metastin-10 is the minimal bioactive sequence of genetic products of KISS1. Clinicopathological analysis of 92 endometrial cancers revealed overall survival is improved in cancers with high expression of GPR54. Through RNAi and mousemodel analyses, metastin-10 was predicted to suppress invasion and metastasis of GPR54-expressing endometrial cancers. These data suggest that metastin-10 may induce genetic changes in the metastatic character of endometrial cancers.
2010-11-18 | GSE25458 | GEO
Project description:Metastasis suppressor genes (MSGs) have contributed to an understanding of regulatory pathways unique to the lethal metastatic process. When re-expressed in experimental models, MSGs block cancer spread to, and colonization of distant sites without affecting primary tumor formation. On a single MSG basis, genes have been identified with expression patterns inverse to a MSG, and found to encode functional, druggable signaling pathways. We now hypothesize that common signaling pathways mediate the effects of many MSGs. By gene expression profiling of human MCF7 breast carcinoma cells expressing a scrambled siRNA or siRNAs to each of 19 validated MSGs (NME1, BRMS1, CD82, CDH1, CDH2, CDH11, CASP8, MAP2K4, MAP2K6, MAP2K7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEBP1, RRM1, KISS1), we identified genes whose expression was significantly opposite to at least five MSGs. We used microarrays to evaluate the modification in gene expression profile after donregulation of multiple metastasis suppressors (NME1, BRMS1, CD82, CDH1, CDH2, CDH11, CASP8, MAP2K4, MAP2K6, MAP2K7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEBP1, RRM1, KISS1) in the breast cancer cell line, MCF7. MCF7 cell line was transfected with siRNA targeting each of 19 metastasis suppressors (NME1, BRMS1, CD82, CDH1, CDH2, CDH11, CASP8, MAP2K4, MAP2K6, MAP2K7, MAPK14, GSN, ARHGDIB, AKAP12, DRG1, CD44, PEBP1, RRM1, KISS1). Two siRNA sequences (siRNA1 and siRNA2) were used for each metastasis suppressor. Two time points (48hr and 96hr) were considered as end of transfection in order to measure early and late effects of the metastasis suppressors downregulation.
2013-12-27 | E-GEOD-53668 | biostudies-arrayexpress
Project description:Global gene expression patterns associated with early stage endometrial cancer have been reported, but changes in molecular expression associated with tumor grade, depth of myometrial invasion, and non-endometrioid histology have not been previously elucidated. Our group hypothesized there are unique genetic events underlying early endometrial carcinogenesis. Ninety-two samples of pathologically reviewed stage I endometrial cancers (80 endometrioid and 12 serous) with a heterogeneous distribution of grade and depth of myometrial invasion (i.e. 9 IAG1, 14 IAG2, 7 IAG3, 14 IBG1, 12 IBG2, 13 IBG3, 7 ICG1, 10 ICG2, and 6 ICG3) were examined in relation to 12 samples of atrophic endometrium from postmenopausal women. Specimens were analyzed using oligonucleotide microarray analysis and a subset of the differentially expressed transcripts was validated using quantitative PCR. Comparison of early stage cancers with normal endometrium samples by the univariate t-test with 10,000 permutations identified 900 genes that were differentially regulated by at least 4-fold at a p value of <0.001. Unsupervised analysis revealed that when compared to normal endometrium, serous and endometrioid stage I cancers appeared to have similar expression patterns. However, when compared in the absence of normal controls, they were distinct. Differential expression analysis revealed a number of transcripts that were common as well as unique to both histologic types. This data uncovers previously unrecognized, novel pathways involved in early stage endometrial cancers and identifys targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes. Ninety-one samples of pathologically reviewed stage I endometrial cancers (79 endometrioid and 12 serous) with a heterogeneous distribution of grade and depth of myometrial invasion (i.e. 9 IAG1, 14 IAG2, 7 IAG3, 14 IBG1, 12 IBG2, 13 IBG3, 7 ICG1, 10 ICG2, and 6 ICG3) were examined in relation to 12 samples of atrophic endometrium from postmenopausal women. Specimens were analyzed using oligonucleotide array analysis.
2011-12-13 | E-GEOD-17025 | biostudies-arrayexpress
Project description:Objectives: The aim of this study was to identify the dysregulated genes involved in tumorigenesis, invasion, and metastasis of endometrial endometrioid adenocarcinoma (EEC). Materials and methods: Surgical specimens of endometrial tissues were obtained from 20 patients with normal endometrium (NEM), 20 patients with atypical endometrial hyperplasia (AEH), and 169 patients with EEC. The expression profiles of NEM, AEH, and EEC were compared by using GeneChip Array. The expression of dysregulated genes was first validated by semi-quantitative reverse transcriptase PCR (SQ RT-PCR). The gene expression levels were determined by real time reverse transcriptase PCR (RTQ RT-PCR) in 85 EEC patients as the training test and 84 EEC patients as the testing test. The protein expressions were then examined by immunohistochemical (IHC) staining. The correlations between the expression of dysregualted genes and clinico-pathologic parameters such as tumorigenesis, invasion, and metastasis of EEC were finally evaluated. Results: Seven dysregulated genes were identified by SQ RT-PCR after microarray analysis. Conclusions: uPA is a dysregulated gene in the tumorigenesis of endometrial carcinomas. The gene expression between tissues from NEM, AEH, and EEC were analyzed by microarray. The samples were grouped according to clinical stages but selected at random from our list of banked, frozen tissues. Ten NEM, 10 AEH, and 20 EEC of early and advanced stages were used for microarray experiments (Group 1: early-staged (stages I and II) EEC (n=10), Group 2: advanced-staged EEC (stages III and IV) (n=10)). Samples were pooled in equimolar amounts (10 samples / pool) for microarray analysis.
2016-01-18 | E-GEOD-39099 | biostudies-arrayexpress
Project description:Endometrial cancer is the most commonly diagnosed gynecologic malignancy in women after breast, lung and colorectal cancer. Despite numerous scientific advances, the incidence and mortality rate of endometrial cancer is on the rise. Considerable research effort has therefore been placed on understanding the pathogenesis of this disease to combat this growing issue. There is now emerging evidence to suggest a putative role for dysregulation of the renin angiotensin system (RAS) and in particular the (pro)renin receptor ((P)RR), in the ontogenesis of endometrial cancer. Support for this notion arises from previous literature implicating (P)RR in cancer pathophysiology (e.g., breast cancer and pancreatic carcinoma) by virtue of its role in proliferation, angiogenesis, fibrosis, migration and invasion. In view of these data, we aimed to investigate the functional role of (P)RR in human endometrial cancer progression and development. To this end, we employed an siRNA-mediated knock down approach to abrogate (P)RR expression in the immortalized endometrial epithelial cell lines; Ishikawa, AN3CA and HEC-1A to explore the role of (P)RR in cellular proliferation and cellular viability. To further extend these analyses we also carried out a sophisticated proteomic screen, that investigated the potential pathways via which (P)RR is acting in endometrial cancer physiology. These data confirmed that (P)RR is critical for endometrial cell cancer development, contributing to both its proliferative capacity and in the maintenance cell viability. This is likely mediated through proteins such as MGA, SLC4A7, SLC7A11 or DHRS2, which were reduced following (P)RR knockdown. These putative protein interactions/pathways, which rely on the presence of (P)RR, are likely to contribute to endometrial cancer progression and could therefore, represent several novel therapeutic targets in the treatment of this cancer. Finally we contend that (P)RR, in its soluble form (s(P)RR) in blood, may have substantial potential as a novel biomarker for cancer diagnosis and prognosis prediction going forward.
2022-04-23 | PXD023042 | Pride
Project description:E-cadherin (E-cad) mediates cell-cell adhesion and has been proposed to suppress both invasion and metastasis. However, invasive ductal cancers retain E-cad expression in the primary tumor, circulating tumor cells, and distant metastases. We recently demonstrated that cancer cell clusters are efficient metastatic seeds. Since clusters organize through cell-cell adhesion, we tested the requirement for E-cad in genetically engineered mouse models of luminal and basal breast cancer. Loss of E-cad increased invasion and dissemination in 3D culture and in the mammary gland. However, E-cad loss also reduced cancer cell proliferation, survival, tumor cell seeding, and metastatic outgrowth in the lungs. At the transcript level, loss of E-cad was associated with increased apoptosis. Consistent with these results, inhibition of apoptosis partially rescued the metastatic phenotype of E-cad null cancer cells. We therefore propose that E-cad is an invasion suppressor, survival factor, and metastasis promoter in invasive ductal cancers.
2019-06-24 | GSE114011 | GEO
Project description:Homeodomain-interacting protein kinase 2 (HIPK2), a well-known tumor suppressor, exhibits contradictory expression patterns in different cancers. This study was performed to reveal the potential mechanism of HIPK2 involvement in oral squamous cell carcinoma (OSCC) metastasis. High throughput RNA-sequencing was used to detect the dysregulated signaling pathways in HIPK2 deficiency OSCC cells. Transwell assay and lymphatic metastatic orthotopic mouse model assay were performed to identify the effect of HIPK2 on tumor invasion. Western blotting and luciferase reporter assay were performed to examine the HIPK2/P53/E-Cadherin axis in OSCC. We observed that depletion of HIPK2 promoted tumor cell invasion in vitro and facilitated cervical lymph node metastasis in vivo. According to mRNA-sequencing, pathways closely related to tumor invasion were notably activated. HIPK2 was found to trigger E-Cadherin expression by mediating P53, which directly targets the CDH1 (coding E-Cadherin) promoter. Restoring P53 expression rescued the E-Cadherin suppression induced by HIPK2 deficiency. Together, the depletion of HIPK2 expression promoted OSCC metastasis by suppressing the P53/E-Cadherin axis, which might be a promising target for anti-cancer therapies.
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Project description:Global gene expression patterns associated with early stage endometrial cancer have been reported, but changes in molecular expression associated with tumor grade, depth of myometrial invasion, and non-endometrioid histology have not been previously elucidated. Our group hypothesized there are unique genetic events underlying early endometrial carcinogenesis. Ninety-two samples of pathologically reviewed stage I endometrial cancers (80 endometrioid and 12 serous) with a heterogeneous distribution of grade and depth of myometrial invasion (i.e. 9 IAG1, 14 IAG2, 7 IAG3, 14 IBG1, 12 IBG2, 13 IBG3, 7 ICG1, 10 ICG2, and 6 ICG3) were examined in relation to 12 samples of atrophic endometrium from postmenopausal women. Specimens were analyzed using oligonucleotide microarray analysis and a subset of the differentially expressed transcripts was validated using quantitative PCR. Comparison of early stage cancers with normal endometrium samples by the univariate t-test with 10,000 permutations identified 900 genes that were differentially regulated by at least 4-fold at a p value of <0.001. Unsupervised analysis revealed that when compared to normal endometrium, serous and endometrioid stage I cancers appeared to have similar expression patterns. However, when compared in the absence of normal controls, they were distinct. Differential expression analysis revealed a number of transcripts that were common as well as unique to both histologic types. This data uncovers previously unrecognized, novel pathways involved in early stage endometrial cancers and identifys targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.
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2012-02-14 | E-GEOD-35801 | biostudies-arrayexpress
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