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Gene expression profiling of triple negative breast cancer, normal ductal cells, and normal tissues

ABSTRACT: To identify novel molecular targets for triple negative breast cancer (TNBC), we have employed whole genome microarray expression profiling. We purified 30 surgically resected breast cancer tissue diagnosed triple negative by means of immunohistochemical staining and 13 normal mammary ductal cells with lasermicrobeam microdissection system (PALM MicroBeam, Carl Zeiss MicroImaging Co., Ltd), performed whole human genome microarray, and compared gene expression levels of TNBC, normal mammary ductal cells, and normal vital organs to develop molecular targets with a minimum risk.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38959 | GEO | 2012/12/21

SECONDARY ACCESSION(S): PRJNA169423

REPOSITORIES: GEO

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Gene expression profiling of triple negative breast cancer, normal ductal cells, and normal tissues

Project description:To identify novel molecular targets for triple negative breast cancer (TNBC), we have employed whole genome microarray expression profiling. We purified 30 surgically resected breast cancer tissue diagnosed triple negative by means of immunohistochemical staining and 13 normal mammary ductal cells with lasermicrobeam microdissection system (PALM MicroBeam, Carl Zeiss MicroImaging Co., Ltd), performed whole human genome microarray, and compared gene expression levels of TNBC, normal mammary ductal cells, and normal vital organs to develop molecular targets with a minimum risk. Gene expression levels of 30 TNBC, 13 normal mammary ductal cells, and 4 normal vital tissues were evaluated. to clarify the molecular mechanism involved in TNBC, we analyzed gene expression profiles of 30 TNBC as well as 13 normal epithelial ductal cells purified by laser microbeam microdissection, and identified 301 transcripts that were significantly up-regulated and 321 transcripts that were significantly down-regulated in TNBC. In addition, gene-expression profiles analysis of normal human vital organs including heart, lung, liver, and kidney allowed us to identify 90 cancer-specific genes involved in breast carcinogenesis such as NEK2, PBK, DTL, MELK and GPSM2. Among them, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC.

2012-12-21 | E-GEOD-38959 | biostudies-arrayexpress

BCL11A: A Novel Breast Cancer Gene which Plays a Critical Role in Mammary Stem Cells and Progenitors

Project description:Triple negative breast cancer (TNBC) has poor prognostic outcome compared to other types of breast cancer1. At present the molecular and cellular mechanisms underlying TNBC pathology are not well understood1. Here we report that the transcription factor BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC) and that its genomic locus is amplified in up to 38% of BLBC tumours. BCL11A overexpression in immortalised human breast epithelial cells promotes tumour formation in xenograft models, whereas knockdown of BCL11A in TNBC cell lines suppresses their tumourigenic potential. In the DMBA-induced mouse mammary tumour model, Bcl11a is found to be essential for tumourigenesis since deletion of Bcl11a before DMBA treatment substantially decreases tumour formation, even in p53-null cells, and inactivation of Bcl11a in established tumours causes their regression. At the cellular level, BCL11A overexpression enhances clonogenicity in vitro whereas its deletion in the mouse causes a reduction in the number of mammary epithelial stem and progenitor cells. Thus, BCL11A has an important role in the genesis of TNBC and in normal mammary epithelial cells. This study highlights the importance of further investigation of BCL11A in breast cancer diagnosis and targeted therapies. [Mouse] KO is bcl11a deleted mammary stem cells. WT are mammary stem cells with intact Bcl11a. [Human] HMLE tumors overexpressing BCL11A.

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Molecular signatures of in-situ to invasive progression for basal-like breast cancers: An integrated mouse model and human tumor study [mouse]

Project description:This study identifies progression in breast ductal carcinoma in situ (DCIS) as it progresses towards triple negative invasive breast cancer (TNBC).

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Molecular signatures of in-situ to invasive progression for basal-like breast cancers: An integrated mouse model and human tumor study [human]

Project description:This study identifies progression in breast ductal carcinoma in situ (DCIS) as it progresses towards triple negative invasive breast cancer (TNBC).

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Molecular signatures of in-situ to invasive progression for basal-like breast cancers: An integrated mouse model and human tumor study [CGH]

Project description:This study identifies progression in breast ductal carcinoma in situ (DCIS) as it progresses towards triple negative invasive breast cancer (TNBC). Bulk DNA arrayCGH was performed on the C3Tag genetically engineered mouse model that forms human breast-like DCIS and TNBC.

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Laser capture microdissection and miRNA expression profiling of different tissue morphologies in triple-negative breast cancer

Project description:Triple negative breast cancers (TNBC) are a morphologically and genetically heterogeneous group of breast cancers with uncertain prediction of biological behavior and response to therapy. The aim of our study was to analyze miRNAs expression within areas of TNBCs with different cellular morphology. We performed laser capture microdissection with PALM MicroBeam system from Zeiss and subsequent expression profiling with Affymetrix GeneChip miRNA 4.0 Arrays to identify distinct classes of miRNAs deregulated in respective tissue morphologies. The study was approved by the Ethics Committee of the University Hospital Olomouc and Medical Faculty of Palacky University in compliance with the Helsinki Declaration (Ref No. 111/15). According to the Czech Law (Act. no. 373/11, and its amendment Act no. 202/17), it is not necessary to obtain informed consent in fully anonymised retrospective studies on formalin-fixed paraffin-embedded tissues. At least one tissue block for each patient was retained in the archive to allow future clinical use such as re-evaluation or further studies.

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BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells

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Transcriptome analysis of Scramble control and Cdk14-sh mouse mammary basal cells

Project description:Wnt/β-catenin signaling pathway has become a key signaling pathway regulating mammary organogenesis and oncogenesis. However, the therapeutic methods by targeting Wnt pathway against breast cancer has been limited. To address this challenge, we investigated the function of cyclin-dependent kinase 14 (CDK14), a member of Wnt signaling pathway, in mammary development and breast cancer progression. We showed that CDK14 was expressed in the mammary basal layer and elevated in triple negative breast cancer (TNBC). CDK14 knockdown reduces colony formation ability and regeneration capacity of mammary basal cells, and significantly inhibits murine MMTV-Wnt-1 basal-like mammary tumor progression. Excitingly, knockdown of CDK14 or pharmacological inhibition of CDK14 by FMF-04-159-2 significantly inhibited the progression and metastasis of human TNBC. Mechanistically, CDK14 inhibition inhibits mammary regeneration and TNBC progression by attenuating Wnt/β-catenin signaling. Together, we demonstrated that CDK14 regulates mammary regeneration and breast tumorigenesis, and is a promising therapeutic target for TNBC.

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