Unknown,Transcriptomics,Genomics,Proteomics

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Increased expression of Bcl11b in human transformed T cell lines leads to chemoresistance accompanied by G1 accumulation.

ABSTRACT: ABSTRACT Background: The expression of BCL11B has been reported in normal and transformed cells derived from T-lymphocytes, neurons, keratinocytes and recently in a subset of squamous cell carcinomas. Despite the rapidly accumulating knowledge concerning Bcl11b biology, the contribution of this protein to normal or transformed cell homeostasis remains open. Methodology/Principal Findings: Here, by employing an overexpression strategy and cells endogenously expressing BCL11B we revealed formerly unidentified features of Bcl11b which shed some light on the potential involvement of the protein in tumor maintenance. Two different T cell lines were forced to overexpress BCL11B which resulted in markedly increased resistance to radiomimetic drugs while no influence on death-receptor apoptotic pathway was observed. Apoptosis resistance triggered by BCL11B overexpression was accompanied by a cell cycle delay caused by accumulation of cells at G1. This cell cycle restriction was associated with upregulation of CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors. Moreover, p27 and p130 proteins accumulated and the SKP2 gene encoding a protein of the ubiquitin-binding complex responsible for their degradation was repressed. Furthermore, the expression of the MYCN oncogene was silenced which resulted in significant depletion of the protein in cells expressing high BCL11B levels. Both cell cycle restriction and resistance to DNA-damage-induced apoptosis coincided and required the histone deacetylase binding N-terminal domain of Bcl11b. The sensitivity to genotoxic stress could be restored by the histone deacetylase inhibitor trichostatine A. Conclusions: The data presented here suggest a potential role of BCL11B in tumor survival and encourage developing Bcl11b-inhibitory approaches as a potential tool to specifically target chemoresistant tumor cells. Using a retroviral-vector-based system in Jurkat cells BCL11B overexpression was compared to controls transfected with the empty vector. Of each group one biological replicate was analyzed on one array.

ORGANISM(S): Homo sapiens

SUBMITTER: Maren Depke

PROVIDER: E-GEOD-21382 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:To investigate effects of long-term intake of RPS on gene expression in the colon and liver of pigs,thirty-six Duroc × Landrace × Large White growing barrows were randomly allocated to corn starch (CS) and RPS groups. Each group consisted of six replicates (pens), with three pigs per pen. Pigs in the CS group were offered a corn/soybean-based diet, while pigs in the RPS group were put on a diet in which 230 g/kg (growing period) or 280 g/kg (finishing period) purified corn starch was replaced with purified RPS during a 100-day trial. Liver transcriptomic results showed that the expression of CD36, CPT1B and ACADM was down-regulated, while AGPAT4, GPAT, FABP1 and FABP3 were up-regulated by the RPS diet, indicating a decrease in fatty acid intake and synthesis, and an increase in fatty acid oxidation and glycerophospholipid synthesis.Analysis of the colonic transcriptome profiles revealed that the RPS diet changed the colonic expression profile of the host genes mainly involved in immune response pathways. RPS significantly increased proinflammartory cytokine IL-1? gene expression and suppressed genes involved in lysosome. Thirty-six Duroc × Landrace × Large White growing barrows (70 days of age, 23.78 ± 1.87 kg) were randomly allocated to two groups, each group consisting of three pigs per pen, and six replicates. Pigs in the control group were offered a corn/soybean-based diet, while 230 g/kg purified corn starch (CS) was replaced with purified RPS in the RPS diet group. Diets were formulated according to the nutrient requirements of the National Research Council (1998). When animals reached the age of 120 days, diets were adapted to the nutrient requirements of the animals (finishing diet) and the amount of purified starch increased to 280 g of CS or RPS per kilogram of feed. Pigs had unlimited access to feed and water throughout the experimental period, which consisted of two 50-day trials in which the pigs consumed the growing diet (days 0-50) and finishing diet (days 51-100), respectively. On day 100, one pig from each replicate that met the target slaughter weight (105 to 110 kg) was slaughtered. The liver and colonic mucosa tissues were collected and preserved in liquid nitrogen for gene expression analysis.

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Increased expression of Bcl11b in human transformed T cell lines leads to chemoresistance accompanied by G1 accumulation.

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