Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast.
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ABSTRACT:
SUBMITTER: Sens-Abuazar C
PROVIDER: S-EPMC3323933 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundResistance to human epidermal growth factor receptor-2 (HER2)-targeted therapies is common, and results in treatment failure and new tumor progression. C35 is over-expressed in many invasive breast cancer endogenously, and functions as an oncogene in breast cancer cell lines.MethodsThe current study aims to investigate effects of C35 on cell viability and migration of HER2-positive breast tumor cells and explore possible mechanisms. The protein expression of C35 in BT-474 breast ductal carcinoma cells was interfered by siRNAs. MTT assay was utilized to detect the viability of BT474 breast ductal carcinoma cells after transfection. The migration of BT474 breast ductal carcinoma cells was examined by cell wound scratch assay.ResultsIn addition, the protein expression of C35, HER2, AKT and p-AKT in breast ductal carcinoma cells were detected by Western Blot. The protein expression of C35 was weaker in siRNA1 and siRNA2 groups compared with the control group. The relative expression ratio of C35 to ?-actin decreased significantly in siRNA2 and siRNA1 groups. When C35 expression was interfered by siRNA1 and siRNA2 for 48 h, the viability of BT474 breast ductal carcinoma cells decreased compared with the control group. In addition, the migration of breast ductal carcinoma cells decreased when C35 expression was interfered by siRNA1 for 24 h, and interfered by siRNA1 and siRNA2 for 48 h.
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Project description:To obtain insight into the molecular basis of ductal carcinoma in situ (DCIS) and its progression by infiltrating surrounding tissue, we have performed cellular-based gene expression analysis of pure DCIS and DCIS with co-existing invasive ductal carcinoma (IDC) and compared the histological and molecular aspects between these morphologically identical lesions seeking to find key genes involved in DCIS progression. For that, 30 samples were evaluated, 4 non-neoplastic (N), 5 pure DCIS, 11 DCIS with co-existing IDC (DCIS-IDC) and 10 IDC. All samples were laser capture microdissected and RNAs were amplified using T7-based methodology. Microarray technology was performed using a customized cDNA platform containing 4,608 human genes. To classify the 4 sample groups according to molecular similarity we performed comparisons of their general expression pattern using ANOVA test (pFDR<0,01) followed by Tukey´s test (fold>l2l). Among the 4 sample groups, as expected, non-neoplastic cells reported the most distinct gene expression pattern. However, among the 3 groups of neoplastic cells, in contrast to morphological aspects, pure DCIS had the most distinct expression profile when compared to the other lesions: DCIS-IDC and IDC. Additionally, by comparison among pure DCIS, DCIS-IDC and N, we identified 147 genes potentially involved in DCIS progression. Unsupervised hierarchical cluster based on expression profile of this gene-set could discriminate DCIS-IDC from 60% of pure DCIS samples. Keywords: disease state analysis Fresh-frozen human breast samples were retrieved from the Tumor Tissue Biobank of the Medical and Research Center - Hospital A. C. Camargo, São Paulo. This research was approved by Ethic Committee of the Medical and Research Center - Hospital A. C. Camargo under number 587/04 and a written informed consent signed by all participants. All patients had presented at least 5 years of follow-up. Thirty samples were evaluated, 4 non-neoplastic breast samples (MN), 5 pure DCIS (stage 0; DCIS-0), 11 DCIS with co-existing IDC (DCIS) and 10 IDC. The non-neoplastic samples were obtained from perilesional mammary specimens from patients submitted to resection of benign lesions. All cells types were laser capture microdissected using PixCell II LCM system (Arcturus Engineering, Mountain View, CA). The total RNA was extracted by using the PicoPureä RNA Isolation kit (Arcturus Engineering # KT0204). A two-round linear amplification procedure based on T7-driven amplification was carried out. Amplified RNA was then used in a transcriptase reverse reaction into cDNA in the presence of Cy3- or Cy5-labeled dCTP. HB4a normal luminal epithelial mammary cell line (O’Hare et al 1991) was amplified following the same protocol and used as reference for microarray hybridizations. Dye swap was performed for each sample analyzed and used as replicate samples. For the raw_data (lowess_data), see Web Link below.
| S-ECPF-GEOD-11042 | biostudies-other
Project description:Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression. Tumor and matching stroma were profiled for 9 DCIS patients, 10 IBC patients, and 3 normal breast. Differential gene expression was evaluated for paired normal stroma versus normal epitelium samples, paired DCIS stroma versus DCIS epitelium samples, paired IBC stroma versus IBC epitelium, IBC stroma versus DCIS stroma, and IBC epithelium versus DCIS epithelium.
| S-ECPF-GEOD-33692 | biostudies-other
Project description: Not available
| S-EPMC7140215 | biostudies-literature
Project description:Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that is separated from the breast stroma by an intact layer of basement membrane and myoepithelial cells. DCIS is a non-obligate precursor of invasive breast cancer, and up to 40% of these lesions progress to invasive disease if untreated. Currently, it is not possible to predict accurately which DCIS would be more likely to progress to invasive breast cancer as neither the significant drivers of the invasive transition have been identified, nor has the clinical utility of tests predicting the likelihood of progression been demonstrated. Although molecular studies have shown that qualitatively, synchronous DCIS and invasive breast cancers are remarkably similar, there is burgeoning evidence to demonstrate that intra-tumor genetic heterogeneity is observed in a subset of DCIS, and that the process of progression to invasive disease may constitute an 'evolutionary bottleneck', resulting in the selection of subsets of tumor cells with specific genetic and/or epigenetic aberrations. Here we review the clinical challenge posed by DCIS, the contribution of the microenvironment and genetic aberrations to the progression from in situ to invasive breast cancer, the emerging evidence of the impact of intra-tumor genetic heterogeneity on this process, and strategies to combat this heterogeneity.
| S-EPMC5528459 | biostudies-other
Project description:To obtain insight into the molecular basis of ductal carcinoma in situ (DCIS) and its progression by infiltrating surrounding tissue, we have performed cellular-based gene expression analysis of pure DCIS and DCIS with co-existing invasive ductal carcinoma (IDC) and compared the histological and molecular aspects between these morphologically identical lesions seeking to find key genes involved in DCIS progression. For that, 30 samples were evaluated, 4 non-neoplastic (N), 5 pure DCIS, 11 DCIS with co-existing IDC (DCIS-IDC) and 10 IDC. All samples were laser capture microdissected and RNAs were amplified using T7-based methodology. Microarray technology was performed using a customized cDNA platform containing 4,608 human genes. To classify the 4 sample groups according to molecular similarity we performed comparisons of their general expression pattern using ANOVA test (pFDR<0,01) followed by Tukey´s test (fold>l2l). Among the 4 sample groups, as expected, non-neoplastic cells reported the most distinct gene expression pattern. However, among the 3 groups of neoplastic cells, in contrast to morphological aspects, pure DCIS had the most distinct expression profile when compared to the other lesions: DCIS-IDC and IDC. Additionally, by comparison among pure DCIS, DCIS-IDC and N, we identified 147 genes potentially involved in DCIS progression. Unsupervised hierarchical cluster based on expression profile of this gene-set could discriminate DCIS-IDC from 60% of pure DCIS samples. Keywords: disease state analysis Fresh-frozen human breast samples were retrieved from the Tumor Tissue Biobank of the Medical and Research Center - Hospital A. C. Camargo, São Paulo. This research was approved by Ethic Committee of the Medical and Research Center - Hospital A. C. Camargo under number 587/04 and a written informed consent signed by all participants. All patients had presented at least 5 years of follow-up. Thirty samples were evaluated, 4 non-neoplastic breast samples (MN), 5 pure DCIS (stage 0; DCIS-0), 11 DCIS with co-existing IDC (DCIS) and 10 IDC. The non-neoplastic samples were obtained from perilesional mammary specimens from patients submitted to resection of benign lesions. All cells types were laser capture microdissected using PixCell II LCM system (Arcturus Engineering, Mountain View, CA). The total RNA was extracted by using the PicoPureä RNA Isolation kit (Arcturus Engineering # KT0204). A two-round linear amplification procedure based on T7-driven amplification was carried out. Amplified RNA was then used in a transcriptase reverse reaction into cDNA in the presence of Cy3- or Cy5-labeled dCTP. HB4a normal luminal epithelial mammary cell line (O’Hare et al 1991) was amplified following the same protocol and used as reference for microarray hybridizations. Dye swap was performed for each sample analyzed and used as replicate samples. For the raw_data (lowess_data), see Web Link below.
2008-04-04 | E-GEOD-11042 | biostudies-arrayexpress
Project description:The mechanisms that drive ductal carcinoma in situ (DCIS) progression to invasive cancer are not clear. Studying DCIS progression in humans is challenging and not ethical, thus necessitating the characterization of an animal model that faithfully resembles human disease. We have characterized a canine model of spontaneous mammary DCIS and invasive cancer that shares histologic, molecular, and diagnostic imaging characteristics with DCIS and invasive cancer in women. The purpose of the study was to identify markers and altered signaling pathways that lead to invasive cancer and shed light on early molecular events in breast cancer progression and development. Transcriptomic studies along the continuum of cancer progression in the mammary gland from healthy, through atypical ductal hyperplasia (ADH), DCIS, and invasive carcinoma were performed using the canine model. Gene expression profiles of preinvasive DCIS lesions closely resemble those of invasive carcinoma. However, certain genes, such as SFRP2, FZD2, STK31, and LALBA, were over-expressed in DCIS compared to invasive cancer. The over-representation of myoepithelial markers, epithelial-mesenchymal transition (EMT), canonical Wnt signaling components, and other pathways induced by Wnt family members distinguishes DCIS from invasive. The information gained may help in stratifying DCIS as well as identify actionable targets for primary and tertiary prevention or targeted therapy.
| S-EPMC7072653 | biostudies-literature
Project description:To obtain insight into the molecular basis of ductal carcinoma in situ (DCIS) and its progression by infiltrating surrounding tissue, we have performed cellular-based gene expression analysis of pure DCIS and DCIS with co-existing invasive ductal carcinoma (IDC) and compared the histological and molecular aspects between these morphologically identical lesions seeking to find key genes involved in DCIS progression. For that, 30 samples were evaluated, 4 non-neoplastic (N), 5 pure DCIS, 11 DCIS with co-existing IDC (DCIS-IDC) and 10 IDC. All samples were laser capture microdissected and RNAs were amplified using T7-based methodology. Microarray technology was performed using a customized cDNA platform containing 4,608 human genes. To classify the 4 sample groups according to molecular similarity we performed comparisons of their general expression pattern using ANOVA test (pFDR<0,01) followed by Tukey´s test (fold>l2l). Among the 4 sample groups, as expected, non-neoplastic cells reported the most distinct gene expression pattern. However, among the 3 groups of neoplastic cells, in contrast to morphological aspects, pure DCIS had the most distinct expression profile when compared to the other lesions: DCIS-IDC and IDC. Additionally, by comparison among pure DCIS, DCIS-IDC and N, we identified 147 genes potentially involved in DCIS progression. Unsupervised hierarchical cluster based on expression profile of this gene-set could discriminate DCIS-IDC from 60% of pure DCIS samples. Keywords: disease state analysis
2008-04-05 | GSE11042 | GEO
Project description:Ductal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression. Tumor and matching stroma were profiled for 9 DCIS patients, 10 IBC patients, and 3 normal breast. Differential gene expression was evaluated for paired normal stroma versus normal epitelium samples, paired DCIS stroma versus DCIS epitelium samples, paired IBC stroma versus IBC epitelium, IBC stroma versus DCIS stroma, and IBC epithelium versus DCIS epithelium.
2012-03-31 | E-GEOD-33692 | biostudies-arrayexpress
Project description:Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the intrinsic molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients. Breast cancer samples, 31 pure DCIS patients, 36 IDC patients, 42 mixed and 6 normal.
| S-ECPF-GEOD-26304 | biostudies-other