To identify metastasis suppressor genes, which are functionally compromised in late-stage breast cancer, we compared the gene expression profiles of an established breast cancer progression cell line model and leveraged large amounts of publically available data by applying multiple bioinformatics filters. Here we report the identification of serum deprivation response (SDPR, also known as cavin-2) as a bona fide metastasis suppressor, capable of impairing the metastatic growth of cancer cells while having no effect on the growth of primary tumors.
SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis.
Disease, Disease stage, Cell line
View SamplesIn this study, we took advantage of a previously established breast cancer progression cell line model system, which consists of a parental MCF10A (MI) spontaneously immortalized mammary epithelial cell line and two of its derivatives: 1) MCF10ATk.cl2 (MII), a MCF10A H-Ras transformed cell line and 3) MCF10CA1h (MIII), derived from a xenograft of the MII cells in nude mice that progressed to carcinoma (1, 2). These cell lines were previously reported to exhibit distinct tumorigenic properties when re-implanted in nude mice; MI is non-tumorigenic, MII forms benign hyperplastic lesions and MIII forms low-grade, well differentiated carcinomas (2, 3). The advantage of this system is that these cell lines were derived from a common genetic background (MCF10A) and accumulated distinct genetic/epigenetic alterations in vivo enabling them to acquire a range of non-tumorigenic to carcinogenic properties. Our initial studies showed that MIII cells, but not MI or MII, exhibit an EMT phenotype, promoter DNA hypermethylation of epithelial genes and highly invasive properties in vitro.
Smad signaling is required to maintain epigenetic silencing during breast cancer progression.
Cell line
View SamplesTBR-760 (formerly BIM-23A760) is a chimeric dopamine (DA)-somatostatin (SST) compound with potent agonist activity at both DA type 2 (D2R) and SST type 2 (SSTR2) receptors. Non-functioning pituitary adenomas (NFPAs) express both D2R and SSTR2 and, consequently, may respond to TBR-760. We utilized a mouse model with the pro-opiomelanocortin (POMC) gene knocked-out that spontaneously develops aggressive NFPAs. Both genomic microarray and DA and SST receptor mRNA expression analysis indicate that POMC KO mouse tumors and human NFPAs have similar expression profiles, establishing POMC KO mice as a valid model for study of NFPAs. Treatment with TBR-760 for 8 weeks resulted in nearly complete inhibition of established tumor growth, whereas tumors from vehicle-treated mice increased in size by 890 ± 0.7%. These results support the development of TBR-760 as a therapy for patients with NFPA.
TBR-760, a Dopamine-Somatostatin Compound, Arrests Growth of Aggressive Nonfunctioning Pituitary Adenomas in Mice.
Specimen part
View SamplesIL13R2 overexpression promotes metastasis of basal-like breast cancers
Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis.
Specimen part, Cell line, Treatment
View SamplesBasal-like breast cancer (BLBC) cells share phenotypic similarities with cancer stem cells (CSCs) but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC cells are able to establish a niche permissive to the maintenance of CSCs and found that tumor cell-derived periostin (POSTN), a component of the extracellular matrix, as well as a corresponding cognate receptor, integrin v3, are highly expressed in a subset of BLBC cell lines as well as in cancer stem cell-enriched populations. Furthermore, we demonstrated that an intact periostin-integrin 3 signaling axis is required for the maintenance of breast CSCs. POSTN activates the ERK signaling pathway and regulates NF-B-mediated transcription of key cytokines, namely IL6 and IL8, which in turn mediate downstream activation of STAT3. In summary, these findings suggest that BLBC cells have an innate ability to establish a microenvironmental niche supportive of CSCs.
Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells.
Cell line
View SamplesChoroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion. To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction) and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations.
Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocytes of choroideremia patients.
Specimen part, Disease
View SamplesThe long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing kidney. The central thesis is straightforward. The combination of laser capture microdissection (LCM) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing kidney. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene in laser capture microdissected components of the developing kidney. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone.
Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment.
Sex
View SamplesOur laboratory's interest is in understanding the molecular principles that underlie the regional organization of the mammalian metanephric kidney. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian kidney development. The goal of this study is to identify a population of genes that are enriched in the renal vesicle (RV) and its derivatives using Wnt4 mutants.
Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Conversion of human fibroblasts to angioblast-like progenitor cells.
Sex, Specimen part, Cell line
View SamplesWe report a novel technique to reprogram human fibroblasts into endothelial and smooth muscle cells using partial iPSC reprogramming and chemically defined media. Using appropriate media conditions for differentiation of human pluripotent cells to CD34+ vascular progenitor cells, we show that temporary expression of pluripotent transcription factors and treatment with chemically-defined media, will induce differentiation of human fibroblasts to CD34+ vascular progenitor cells. Sorted CD34+ cells can then be directed to differentiate into vascular endothelial cells expressing a variety of smooth muscle markers.
Conversion of human fibroblasts to angioblast-like progenitor cells.
Sex, Specimen part
View Samples