Similar Datasets
Project description:Endometrium-specific Cre-Lox deletion of both Pten and Tp53 via regulation of the progesterone receptor promoter is known to generate a spontaneous carcinogenic mouse model of endometrial cancer. A mouse endometrial cancer cell line, mECC, was established from the uterine carcinoma tumor tissue of its pure strain model generated by backcrossing in C57BL/6 mice. A high-grade endometrial cancer cell line (Highly Progressive mECC: HPmECC) was established by further introducing c-Myc in mECCs. RNA sequencing analysis was performed using cultured HPmECCs and mECCs, as well as primary cultured C57BL/6 normal endometrial cells for assessing the genetic characteristics of HPmECCs.
2022-04-01 | GSE176257 | GEO
Project description:Lynch syndrome (LS), caused by inherited mutations in DNA mismatch repair genes including MSH2, carries a 60% lifetime risk of endometrial cancer (EC). Beyond hypermutability, mechanisms driving LS-associated EC remain unclear. We investigated MSH2 loss in EC pathogenesis using a mouse model (PR-Cre Msh2(LoxP/LoxP), abbreviated Msh2KO), primary cell lines, human tissues, and human EC cells with isogenic MSH2 knockdown. By eight months, 58% of Msh2KO mice developed endometrial atypical hyperplasia (AH), a precancerous lesion. At 12-16 months, 47% exhibited either AH or ECs with histologic similarities to human LS-ECs. Transcriptomic profiling of EC from Msh2KO mice revealed a signature of mitochondrial dysfunction. Subsequent studies in vitro and in vivo revealed mitochondrial dysfunction based upon two mechanisms: reduced mitochondrial content and structural disruptions in retained mitochondria. Human LS-ECs also exhibited reduced mitochondrial content compared to non-LS-ECs. Functional studies demonstrated metabolic reprogramming of MSH2-deficient EC cells, including decreased oxidative phosphorylation and heightened susceptibility to glycolysis suppression. These findings identified mitochondrial dysfunction and metabolic disruption as consequences of MSH2 deficiency in EC. Mitochondrial and metabolic aberrations should be evaluated as biomarkers for endometrial carcinogenesis or risk stratification and represent potential targets for cancer interception in women with LS. To achieve Msh2 loss in the endometrium, we bred progesterone receptor Cre knock-in (PR-Cre) mice to Msh2(LoxP/LoxP) mice to produce PR-Cre+Msh2(LoxP/LoxP) mice with targeted loss of MSH2 expression in tissues that express PR, including the uterus (hereafter abbreviated Msh2KO). Control mice contain Msh2(LoxP/LoxP) without PR-Cre. We profiled Msh2KO endometrial tumors, Msh2KO benign endometrium, and control mouse benign endometrium using transcriptomic profiling of microdissected glands via microarray analysis (ClariomD, Affymetrix).
2025-04-02 | GSE288518 | GEO
Project description:Transcriptome profile of murine endometrial cancer cell lines
| PRJNA489854 | ENA
Project description:Endometrial cancer remains the most common gynecological malignancy in the United States. While the loss of the tumor suppressor, PTEN, is well studied in endometrial cancer, recent studies suggest that DICER1, the endoribonuclease responsible for miRNA genesis, also plays a significant role in endometrial adenocarcinoma. To examine the effects of DICER1 deletion on mRNA and miRNA expression in endometrial cancer, poly-A RNA sequencing (RNA-seq) and small RNA sequencing were performed. Our findings indicate a relationship between appropriate miRNA expression and molecular signaling pathways in the development of poorly-differentiated endometrial adenocarcinoma.
2021-08-03 | GSE155643 | GEO
Project description:Comparison of gene expression in murine Kras mutant (LLC, AE17, MC38, FULA1) and Kras wildtype cell lines (B16F10, PANO2, CULA). First gene expression of benign cells and tissue ( BMDM, TEC, LUNG, BMMC) was subtracted from both Kras mutant or Kras wildtype gene expression profiles. Second Kras mutant gene expression was compared to Kras wildtype gene expression. Cell lines expressing genetically modified Kras gene were included in the analysis. Genetic modification was either done by overexpression of mutant KRAS harboring a G12C mutation or silencing with shRNA targeting Kras. shControl cell lines were used also as wildtype samples in different analysis presented in the manuscript except MC38 ( run on chip MoGene_1.0).
2022-05-02 | GSE130624 | GEO
Project description:We found that in KrasG12D-expressing endometrial organoids, Pten knockdown did not confer tumorigenicity, but Cdkn2a knockdown or Trp53 deletion led to the development of carcinosarcoma (CS), a rare, aggressive tumor comprising both carcinoma and sarcoma.To better characterize the pathogenesis of CS from organoids, we conducted a transcriptome analysis.
2021-06-30 | GSE175512 | GEO
Project description:Murine Kras mutant or Kras wildtype cancer cell lines
| PRJNA540827 | ENA
Project description:To investigate the role of the E3 ubiquitin ligase Thyroid Receptor Interacting Protein 12 (TRIP12) in pancreatic acinar cell identity and pancreatic carcinogenesis, we used genetically engineered mouse models of pancreas-selective Trip12 deletion, mutant Kras (G12D) and mutant P53 (R172H). We performed gene expression analysis using RNA-seq data from adult acinar cells. We established cell lines from murine pancreatic tumors.
2024-04-19 | GSE221587 | GEO
Project description:Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. In order to identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. Keywords: Gene expression profiling RNA was extracted from uterine segments with either CAH or invasive carcinoma from Pten+/-;Mlh1-/- , Pten+/-;Mlh1+/+ and Wild type female mice. The RNA was hybridized to Affymetrix mouse 430A chip in order to determine changes in global gene expression patterns
2008-11-19 | E-GEOD-10866 | biostudies-arrayexpress
Project description:Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify possible mechanisms for these differences, we performed a global genomic survey of amplifications, deletions, and loss of heterozygosity, which identified 11 significantly amplified and 13 significantly deleted regions. Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster. Moreover, samples with PIK3CA amplification carried signatures associated with in vitro activation of PI3 kinase (PI3K), a signature that was shared by aggressive tumors without PIK3CA amplification. Tumors with loss of PTEN expression or PIK3CA overexpression that did not have PIK3CA amplification also shared the PI3K activation signature, high protein expression of the PI3K pathway member STMN1, and an aggressive phenotype in test and validation datasets. However, mutations of PTEN or PIK3CA were not associated with the same expression profile or aggressive phenotype. STMN1 expression had independent prognostic value. The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of the PI3K pathway in patients who have aggressive endometrial cancer. 84 endometrial cancers (including 9 cell lines) were subject to 100K SNP analysis. 57 endometrial cancers were subject to expression analysis.
2009-03-23 | E-GEOD-14860 | biostudies-arrayexpress