Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, in addition to DNA repair, genome stability is also controlled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can alter the DNA damage cell cycle checkpoints. Here, we show that hypoxia (24h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting of U2OS cells. While some of the changes reflected hypoxia-induced inhibition of cell cycle progression, flow cytometric bar-coding analysis of individual cells showed that the levels of several G2 checkpoint regulators were reduced in G2 phase cells after hypoxic exposure, in particular cyclin B1. These effects were accompanied by decreased Cyclin dependent kinase (CDK) activity in G2 phase cells after hypoxia. Furthermore, cells pre-exposed to hypoxia showed a longer G2 checkpoint arrest upon treatment with ionizing radiation. Similar results were found following other hypoxic conditions (~0.03 % O2 20h and 0.2% O2 72h). These results demonstrate that the DNA damage G2 checkpoint can be altered as a consequence of hypoxia, and we propose that such alterations may influence the genome stability of hypoxic tumors.
Hypoxia-induced alterations of G2 checkpoint regulators.
Specimen part, Cell line
View SamplesFoxp1 is expressed throughout B cell development, but the physiological functions in mature B lymphocytes are unknown. We therefore evaluated differential gene expression in Foxp1-deficient B cells, with or
Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells.
Specimen part
View SamplesDepending on the tumor type IB kinase (IKK) can act as tumor promoter or tumor suppressor in various malignancies. Here we demonstrate a key function of IKK in the suppression of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKK kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of IFN expressing M1-like myeloid cells. In IKK mutant mice M1-like polarization is not controlled in a cell autonomous manner but depends rather on the interplay of both IKK mutant tumor epithelia and immune cells.
IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.
Specimen part, Time
View SamplesIn contrast to its inhibitory effects on many cells, IL-10 activates CD8+ tumor infiltrating lymphocytes (TILs) and enhances their antitumor activity. However, how IL-10 globaly regualte TIL CD8+ T cell function is stil not clear. To understand the transcriptional regulation of TIL CD8+ T cell by IL-10, we performed a microarray analysis using in vitro expanded HUMAN LUNG CANCER TIL CD8 T cells with or without IL-10.
Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression.
Specimen part
View SamplesMiR-1246 was found to promote tumorigenesis and metastasis in sevearl cancer types. In the context of tumor microenvironment, tumor-associated macrophages are a central part typically correlated with poor prognosis.
Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246.
Specimen part
View SamplesPrimary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD.
IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View SamplesProstate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes beween AA cancer and patient matched normal tissues.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View SamplesProstate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling analysis using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes in AA and EA patients.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View SamplesProstate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling analysis using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes in EA PCa vs. EA normal.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View Samples