Stress induces undifferentiated stem cells to differentiate in a way that looks like normal differentiation
Hyperosmolar stress induces global mRNA responses in placental trophoblast stem cells that emulate early post-implantation differentiation.
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View SamplesConjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sex, Age, Specimen part
View SamplesOverexpression of fatty acid synthase (FAS) has been reported in both malignant and premalignant breast lesions, and has been associated with poor outcome. FAS has gained interest as a metabolic target for the treatment of breast cancer based on evidence that blockade with the antifungal antibiotic, cerulenin or synthetic inhibitor C75 inhibits proliferation of breast cancer cells and delays tumor development. Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit FAS in bovine mammary adipose. Based on previously well-documented anti-tumor activity of CLA, we hypothesized that one mechanism of CLAs anti-tumorigenic activity may be metabolic blockade of FAS. We fed virgin PyV-MT transgenic mice a diet supplemented with either 1% CLA, as mixed isomers, or control chow for four weeks. Tissue histology was determined by H&E staining. cDNA microarray and real-time quantitative PCR were performed to determine relative expression of lipogenic genes. Western blots were used to examine relative protein expression of FAS. Differences in protein densitometry were analyzed using Students 2-sided T-test. Probability was determined using the binomial sign test. Level of significance for all tests was 0.05. H&E staining revealed a shift towards advanced mammary lesions in the CLA-fed mice compared to control animals (24/26 vs. 11/26) (p for trend < 0.001). Microarray analysis revealed a >2-fold decrease in FAS in the CLA-fed group compared to controls, and was confirmed by quantitative RT-PCR (p < 0.001) and Western blot. The decrease in FAS mRNA expression was unexpectedly associated with more advanced disease (p for trend < 0.01). Conclusions: Dietary CLA suppressed fatty acid synthase in the mammary glands of the PyV-MT mouse while promoting mammary tumor progression.
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Sex, Age, Specimen part
View SamplesTo identify the molecular impact of SPIO nanoparticle inhalation exposure on lung tissue.
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Sex, Specimen part, Treatment
View SamplesMethyl tert-butyl ether (MTBE) has been shown to target developing vasculature in piscine and mammalian model systems. In the zebrafish, MTBE induces vascular lesions throughout development. These lesions result from exposure to MTBE at an early stage in development (6-somites to Prim-5 stages). During this time period, transcript levels of vegfa, vegfc, and vegfr1 were significantly decreased in embryos exposed to 5 mM MTBE.
Manipulation of the HIF-Vegf pathway rescues methyl tert-butyl ether (MTBE)-induced vascular lesions.
Specimen part
View SamplesTwo T7 based methods One round of Amplification (Affymetrix) and Two round of Amplification were compared to two Ribo-SPIA based systems, RiboSPIA and pico Ribo SPIA systems. Data for One Round of amplification , Two round of amplification and RiboSPIA are listed here.
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View SamplesZebrafish have the remarkable ability to regenerate body parts including the heart, spinal cord and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage-larvae also possess the ability to regenerate the caudal fin. A comparative genomic analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of Retinoic acid (RA), as one of the highly induced genes across the three regeneration platforms.
Comparative expression profiling reveals an essential role for raldh2 in epimorphic regeneration.
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View SamplesThe spinal cords of mice submitted to aortic cross-clamping for 7.5 minutes present with gray matter damage and central cord edema. 60% of mice subsequently experience hindlimb and tail paralysis.
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Specimen part
View SamplesCryptorchidism and scrotal heating result in abnormal spermatogenesis but the mechanism(s) proscribing this temperature sensitivity are unknown. It was previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat resistant than the testis from the C57BL/6 strain. We have attempted to probe into the mechanism(s) involved in heat sensitivity by examining global gene expression profiles of normal and heat-treated testes from C57BL/6, AKR/N and MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and 416 transcripts were differentially expressed (at least two-fold higher or lower) when compared to the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts between them. There were 231 transcripts differentially expressed between C57BL/6 and two purported heat-resistant strains, AKR/N and MRL/MpJ-+/+. Next, the testes of C57BL/6 and AKR/N mice were exposed to 43C for 15 min and harvested at different time points for TUNEL studies and microarrays. An increase of TUNEL-positive germ cell numbers was significant 8 hr after heat exposure in the C57BL/6 mouse. However, this increase was not observed in the AKR/N mouse until 10 hr after heat exposure. All tubules showed germ cell loss and disruption in C57BL/6 testis 24 hr after heat shock. In contrast, although a number of seminiferous tubules showed an abnormal morphology 24 hr post-heat shock in the AKR/N mouse, many tubules still retained a normal structure. Numerous transcripts exhibited differential regulation between the two strains within 24 hours after heat exposure. The differentially expressed transcripts in the testes 8 hr after heat exposure were targeted to identify the genes involved in the initial response rather than those due to germ cell loss. Twenty transcripts were significantly down-regulated and 19 genes were up-regulated by hyperthermia in C57BL/6 and did not show a parallel change in the AKR/N testis. Conversely, heat shock resulted in 30 up-regulated transcripts and 31 down-regulated transcripts in AKR/N that were not similarly regulated in C57BL/6. A number of genes shared similar differential expression patterns and differential regulation by hyperthermia in both strains of mice. Taken together, the present study indicates the diverse genetic backgrounds in the three strains lead to major differences in normal testis gene expression profiles while the differences in heat shock responses involves a significantly smaller number of genes. The data generated may provide insights regarding gene networks and pathways involved in heat stress and their relationship to spermatogenesis.
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View SamplesMurine testis developmental time course created from tissue samples collected from birth through adulthood and hybridized to M430_2 chips in duplicate.
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