RPPA_RATHER_ILC
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66647 | GEO | 2015/03/07
SECONDARY ACCESSION(S): PRJNA277536
REPOSITORIES: GEO
Similar Datasets
Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray. Gene expression profiling of 144 ILC breast cancers and 15 ILC cell lines
2016-01-05 | E-GEOD-68057 | biostudies-arrayexpress
Project description:Current immunotherapies are ineffective for estrogen receptor positive (ER+) breast cancers, which account for nearly 70% of all breast cancers. Amongst the ER+ breast cancers, the major subtypes are invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). We utilized droplet-based single-cell RNAseq (10X Genomics) to analyzed the immune landscape of both peripheral blood and tumor infiltrating immune populations in both IDC and ILC. These analyses demonstrated substantial heterogeneity of macrophage within the tumor microenvironment.
2023-01-29 | GSE193911 | GEO
Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray.
2016-01-05 | GSE68057 | GEO
Project description:Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.
2020-06-23 | GSE130650 | GEO
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:One-third of all ER+ breast tumors treated with endocrine therapy fail to respond, and the remainder are likely to relapse in the future. Almost all data on endocrine resistance has been obtained in models of invasive ductal carcinoma (IDC). However, invasive lobular carcinomas (ILC) comprise up to 15% of newly diagnosed invasive breast cancers diagnosed each year and, while the incidence of IDC has remained relatively constant during the last 20 years, the prevalence of ILC continues to increase among postmenopausal women. We report a new model of Tamoxifen (TAM)-resistant invasive lobular breast carcinoma cells that provides novel insights into the molecular mechanisms of endocrine resistance. SUM44 cells express ER and are sensitive to the growth inhibitory effects of antiestrogens. Selection for resistance to 4-hydroxytamoxifen led to the development of the SUM44/LCCTam cell line, which exhibits decreased expression of estrogen receptor alpha (ERα) and increased expression of the estrogen-related receptor gamma (ERRγ). Knockdown of ERRγ in SUM44/LCCTam cells by siRNA restores TAM sensitivity, and overexpression of ERRγ blocks the growth-inhibitory effects of TAM in SUM44 and MDA-MB-134 VI lobular breast cancer cells. ERRγ-driven transcription is also increased in SUM44/LCCTam, and inhibition of activator protein 1 (AP1) can restore or enhance TAM sensitivity. These data support a role for ERRγ/AP1 signaling in the development of TAM resistance, and suggest that expression of ERRγ may be a marker of poor Tamoxifen response.
2008-11-01 | GSE12708 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for LObular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."
2022-08-31 | GSE152360 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for Lobular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."
2022-08-31 | GSE152512 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for Lobular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."
2022-08-31 | GSE152366 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for LObular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."
2022-08-31 | GSE152365 | GEO