Loss of E-cadherin and PTEN induces classical invasive lobular carcinoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB14147 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1535030.fastq.gz | Fastqsanger.gz | |||
| ERR1535040.fastq.gz | Fastqsanger.gz | |||
| ERR1535320_1.fastq.gz | Fastqsanger.gz | |||
| ERR1535320_2.fastq.gz | Fastqsanger.gz | |||
| ERR1535330_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 92 |
Similar Datasets
Project description:Breast cancer tumors: of ductal (D) and classical lobular (L) type. Experiment "BC2_Jeffrey_minus_G50_1" was denoted as BC-D-002.
2007-03-09 | E-SMDB-3963 | biostudies-arrayexpress
Project description:Background: Despite the fact that loss of E-cadherin is causal to the development and progression of invasive lobular breast cancer (ILC), no targeted therapy is available to treat this major breast cancer subtype. This study is aimed at identifying clinically targetable pathways that are aberrantly active downstream of E-cadherin loss in ILC. Methods: Reverse-phase protein array (RPPA) analyses were performed in the context of E-cadherin loss using mouse and human breast cancer cells. A combination of mRNA sequencing, conditioned medium growth assays and CRISPR-Cas9 knock-out experiments were performed to identify and validate activation of oncogenic pathways in ILC. Human ILC samples were employed to validate activation by immunohistochemistry on tissue micro-arrays. Finally, we assessed the effect of pathway inhibition using anoikis resistance and anchorage-dependent growth in vitro. Results: We demonstrate that E-cadherin loss leads to increased activation of FAK and PI3K/AKT signalling. Autocrine activation of growth factor receptor signalling and its downstream PI3K/AKT hub was a direct consequence of E-cadherin loss, independent of activating mutations in either PIK3CA, AKT or PTEN. Analysis of human ILC samples confirmed pathway activity, and pharmacological inhibition of AKT using AZD5363 and MK2206 resulted in robust inhibition of cell growth and survival of ILC cells in anchorage-dependent and independent conditions. Moreover, our results indicate a role for intracellular FAK in the regulation of ILC anoikis resistance. Conclusion: Our data demonstrate that E-cadherin loss evokes additional PI3K/AKT activation independent of oncogenic mutations in this pathway. We propose clinical intervention of PI3K/AKT in ILC based on functional E-cadherin inactivation, irrespective of activating pathway mutations.
2019-03-22 | GSE81977 | GEO
Project description:Breast cancer tumors of ductal (D) and lobular (L) type. Not all lobular tumors are "classical lobular" tumors. Experiment "BC2_Jeffrey_minus_G50_1" was denoted as BC-D-002.
2007-03-27 | E-SMDB-3962 | biostudies-arrayexpress
Project description:Invasive lobular carcinoma (ILC) of the breast accounts for 5-15% of breast cancers and is characterized by loss of E-cadherin and believed to arise via a linear histological progression. Genomic studies have identified a clonal relationship between ILC and concurrent lobular carcinoma in situ (LCIS) lesions, suggesting that LCIS may be a precursor lesion. It has been shown that an LCIS diagnosis confers a 15-20% risk of progression to ILC, over a lifetime. Currently no molecular test or markers can identify LCIS lesions likely to progress to ILC. Since microRNA (miRNA) expression changes have been detected in a number of other cancer types, we explored whether their dysregulation might be detected during progression from LCIS to ILC. Using the Illumina miRNA profiling platform, designed for simultaneous analysis of 470 mature miRNAs, we analyzed the profiles of archived normal breast epithelium, LCIS lesions found alone, LCIS lesions concurrent with ILC, and the concurrent ILCs, as a model of linear histological progression toward ILC. We identified two sets of differentially expressed miRNAs, the first set highly expressed in normal epithelium, including hsa-miR-224, -139, -10b, -450, 140 and -365 and the second set upregulated during lobular neoplasia, including hsa-miR-375, -203, -425-5p, -183, -565 and -182. Using quantitative RT-PCR, we validated a trend of increased expression for hsa-mir-375, hsa-mir-182, and hsa-mir-183 correlating with ILC progression. As we detected increased expression of hsa-miR-375 in LCIS lesions synchronous with ILC, we sought to determine whether hsa-mir-375 might induce phenotypes reminiscent of lobular neoplasia by expressing it in the MCF10A 3D culture model of mammary acinar morphogenesis. Increased expression of hsa-miR-375 resulted in loss of cellular organization and acquisition of a hyperplastic phenotype. These data suggest that dysregulated miRNA expression contributes to lobular neoplastic progression. 6 specimens were analyzed in duplicate. One frozen normal lobular epithelium and the matched FFPE (1 month old) normal lobular epithelium. One lobular carcinoma in situ (LCIS) found alone, one LCIS synchronous with an invasive lobular carcinoma (ILC), the synchronous ILC (from a different archived block), and one ILC found alone without presence of any other breast cancer.
2011-04-11 | E-GEOD-28514 | biostudies-arrayexpress
Project description:Invasive lobular carcinoma (ILC) is an aggressive breast cancer subtype with poor response to chemotherapy. Besides loss of E-cadherin, a hallmark of ILC, genetic inactivation of PTEN is frequently observed in patients. Through concomitant Cre-mediated inactivation of E-cadherin and PTEN in mammary epithelium, we generated a mouse model of classical ILC (CLC), the main histological ILC subtype. While loss of E-cadherin induced cell dissemination and apoptosis, additional PTEN inactivation promoted cell survival and rapid formation of invasive mammary tumors that recapitulate the histological and molecular features, estrogen receptor (ER) status, growth kinetics, metastatic behavior, and tumor microenvironment of human CLC. Combined inactivation of E-cadherin and PTEN is sufficient to cause CLC development. These CLCs showed significant tumor regression upon BEZ235-mediated inhibition of PI3K signaling. In summary, this mouse model provides important insights into CLC development and suggests inhibition of phosphatidylinositol 3-kinase (PI3K) signaling as a potential therapeutic strategy for targeting CLC.
| S-EPMC4999419 | biostudies-literature
Project description:E-cadherin loss induces autocrine activation of oncogenic growth factor signalling in metastatic lobular breast cancer.
| PRJNA323547 | ENA
Project description:Invasive lobular carcinoma (ILC) of the breast accounts for 5-15% of breast cancers and is characterized by loss of E-cadherin and believed to arise via a linear histological progression. Genomic studies have identified a clonal relationship between ILC and concurrent lobular carcinoma in situ (LCIS) lesions, suggesting that LCIS may be a precursor lesion. It has been shown that an LCIS diagnosis confers a 15-20% risk of progression to ILC, over a lifetime. Currently no molecular test or markers can identify LCIS lesions likely to progress to ILC. Since microRNA (miRNA) expression changes have been detected in a number of other cancer types, we explored whether their dysregulation might be detected during progression from LCIS to ILC. Using the Illumina miRNA profiling platform, designed for simultaneous analysis of 470 mature miRNAs, we analyzed the profiles of archived normal breast epithelium, LCIS lesions found alone, LCIS lesions concurrent with ILC, and the concurrent ILCs, as a model of linear histological progression toward ILC. We identified two sets of differentially expressed miRNAs, the first set highly expressed in normal epithelium, including hsa-miR-224, -139, -10b, -450, 140 and -365 and the second set upregulated during lobular neoplasia, including hsa-miR-375, -203, -425-5p, -183, -565 and -182. Using quantitative RT-PCR, we validated a trend of increased expression for hsa-mir-375, hsa-mir-182, and hsa-mir-183 correlating with ILC progression. As we detected increased expression of hsa-miR-375 in LCIS lesions synchronous with ILC, we sought to determine whether hsa-mir-375 might induce phenotypes reminiscent of lobular neoplasia by expressing it in the MCF10A 3D culture model of mammary acinar morphogenesis. Increased expression of hsa-miR-375 resulted in loss of cellular organization and acquisition of a hyperplastic phenotype. These data suggest that dysregulated miRNA expression contributes to lobular neoplastic progression.
2011-04-11 | GSE28514 | GEO
Project description:To explore the mechanisms downstream of NOTCH1 and PTEN in the control of leukemia cell growth, we performed expression profiling on NOTCH1 induced and Pten-positive T-ALL tumor cells infected with constitutively active AKT (myristoylated-AKT). Constitutive activation of AKT rescues the transcriptional programs induced by NOTCH1 inhibition in Pten-positive T-ALL cells We performed microarray gene expression analysis of GSI treatment in Pten WT NOTCH1 induced leukemias infected with constitutively active AKT (myristoylated-AKT) or empty vector.
2015-08-31 | E-GEOD-71089 | biostudies-arrayexpress
Project description:The aim of our study was to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells. We examined ten mastectomy specimens from postmenopausal breast cancer patients. Ductal and lobular tumor and normal cells were microdissected from cryosections. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. GCOS pairwise comparison algorithm and rank products have identified multiple genes that are differentially expressed in comparisons between ductal and lobular tumor and normal cell types. The results suggest that these genes are involved in epithelial-mesenchymal transition, TGFbeta and Wnt signaling. These changes are present in both tumor types but appear to be more prominent in lobular carcinomas. Ten surgical specimens obtained by mastectomy from postmenopausal patients with invasive ductal (IDC) and lobular breast (ILC) carcinomas were investigated. Of these, 5 were IDCs and 5 were ILCs. Tumor and normal tissues from the same mammary gland were identified by an experienced pathologist, snap-frozen in liquid nitrogen and stored at -80ºC for further analysis. Microdissection, RNA isolation, amplification, labeling and microarray analysis are described in sample definitions. Samples from particular cell types (normal ductal, normal lobular, tumor ductal, tumor lobular - 10, 10, 5, 5 samples, respectively) were considered as biological replicates and were compared in between.
2007-11-01 | E-GEOD-5764 | biostudies-arrayexpress
Project description:The aim of our study was to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells. We examined ten mastectomy specimens from postmenopausal breast cancer patients. Ductal and lobular tumor and normal cells were microdissected from cryosections. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. GCOS pairwise comparison algorithm and rank products have identified multiple genes that are differentially expressed in comparisons between ductal and lobular tumor and normal cell types. The results suggest that these genes are involved in epithelial-mesenchymal transition, TGFbeta and Wnt signaling. These changes are present in both tumor types but appear to be more prominent in lobular carcinomas. Keywords: cell type comparison
2007-03-16 | GSE5764 | GEO