Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtypes. Various cell line models have been used to develop gene expression signatures unique to cancer cells that have metastasized to specific organs, although these efforts were not in a uniform setting. In this study, we compared gene expression pattern in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung metastasis (LMD-231), bone metastasis (BMD-231), adrenal metastasis (ADMD-231) and brain metastasis (231-BR) variants grown under the same growth condition. When gene expression differences between metasteses (p value of <0.01) were compared, 231-BR cells showed the highest gene expression difference (633 genes) followed by ADMD-231 (196 genes), LMD-231 (79 genes), and BMD-231 cells (60 genes) compared with other metastatic cells. 231-BR cells specifically overexpressed neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 by more than five fold compared with cells isolated from other sites of metastasis. Ingenuity pathway analysis of differentially expressed genes revealed activation of pathways that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR cells, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-B signaling pathway activation was common to all metastatic cells except BMD-231.To test this possibility, we compared gene expression pattern in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. Between metastatic cells, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. 231-BR cells specifically overexpressed neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1. pathways that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR cells, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-B signaling pathway activation was common to all metastatic cells except BMD-231.
No associated publication
Cell line
View SamplesRabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre) to switch neurons constitutively expressing tdTomato (red) to expression of a Cre-inducible EGFP (green), permanently marking neurons that had been infected in vivo. We were able to isolate these previously infected neurons (infected) by flow cytometry and assayed their gene expression profiles compared to uninfected cells (uninfected) from the same mice.
No associated publication
Specimen part
View SamplesIntervertebral disc degeneration is an important contributor to chronic low back pain. While a wide spectrum of clinically relevant degenerative disc phenotypes have been observed during aging, their molecular underpinning have not been established.
Comparison of inbred mouse strains shows diverse phenotypic outcomes of intervertebral disc aging.
Age, Specimen part
View SamplesIn this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45), across three strains (Fischer, Long Evans and Sprague Dawley). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 119)
No associated publication
Sex, Specimen part, Treatment
View SamplesIn this study, we analyzed the effects of chronic alcohol consumption on liver repair and regeneration after partial hepatectomy (PHx). Rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; corresponding pair-fed calorie-matched controls were fed diets in which ethanol calories were replaced either by carbohydrate or by fat. After 5 weeks, rats were subjected to 70% PHx and liver samples were collected at 1, 6 and 24h after the surgery. The excised liver samples at t=0 served as within-animal controls. We used Affymetrix Rat Gene 1.0 ST arrays to obtain global gene expression data from each liver sample (n=4 replicate rats, 72 arrays total).
Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats.
Specimen part, Time
View SamplesDuctal 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.
Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia.
Specimen part, Subject
View SamplesIn this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 40)
No associated publication
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell cycle-coupled expansion of AR activity promotes cancer progression.
Cell line
View SamplesEvaluation of the genome wide impact of cell cycle position on DHT stimulated gene expression programs. Results show differential cell cycle regulated gene expression in different cell cycle phases.
Cell cycle-coupled expansion of AR activity promotes cancer progression.
Cell line
View SamplesCyclin D1b is a splice variant of the cell cycle regulator Cyclin D1 and is known to harbor divergent and highly oncogenic functions in human disease. While Cyclin D1b is induced during disease progression in many cancer types, the mechanisms underlying Cyclin D1b function remain poorly understood. Herein, models of human disease were utilized to resolve the downstream pathways requisite for the pro-tumorigenic functions of Cyclin D1b. Specifically, it was shown that Cyclin D1b modulates the expression of a large transcriptional network that cooperates with AR signaling to enhance tumor cell growth and invasive potential. Notably, Cyclin D1b promoted AR-dependent activation of genes associated with metastatic phenotypes. Further exploration determined that transcriptional induction of SNAI2 (Slug) was essential for Cyclin D1b- mediated proliferative and invasive properties, implicating Slug as a critical driver of disease progression. Importantly, Cyclin D1b expression highly correlated with that of Slug in clinical samples of advanced disease. Further, in vivo analyses provided strong evidence that Slug enhances both tumor growth and homing to distal soft tissues. Collectively, these findings reveal the underpinning mechanisms behind the pro-tumorigenic functions of Cyclin D1b, and demonstrate that the convergence of the Cyclin D1b-AR and Slug pathways results in the activation of processes critical for the promotion of lethal tumor phenotypes.
Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes.
Specimen part, Cell line
View Samples