Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effects of tenascin-C on gene expression in mouse mammary gland tumor

ABSTRACT: Tenascin-C (TNC), a cancer-associated extracellular matrix glycoprotein, plays a pivotal role in tumor growth. However, the mechanism whereby TNC affects tumor biology remains unclear. We used microarrays to investigate change in global gene expression between tumors in wild-type (WT) mice, which express TNC, and tumors in TNC-knockout (TNKO) mice. We developed a non-TNC-producing mouse mammary tumor cell line (GLMT1). GLMT1 was inoculated in the drosal flank of WT mice and TNKO mice. After 14 days, the tumor were harvested and RNA was extracted. Subsequently, they were processed and hybridized on Affymetrix GeneChip Mouse Genome 430 2.0 Array

ORGANISM(S): Mus musculus

SUBMITTER: Kohei Saeki

PROVIDER: E-GEOD-77739 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: We previously demonstrated that B16F1 melanoma tumors growing in syngeneic germline-deleted TNFR1,2 -/- mice were more sensitive to ionizing radiation (IR) compared to tumors growing in C57BL/6 wild-type mice; however, the mechanisms linked to this difference in radiosensitivity are not fully understood. Methodology/ Principal Findings: We used DNA microarrays to identify alterations in the expression of functional gene clusters associated with the radiosensitization of B16F1 tumors growing in TNFR1,2 -/- mice. At the basal level, disruption of host stromal TNFα signaling resulted in the over-expression of tumor genes involved in extracellular matrix remodeling and angiogenesis. Phenotypically, these tumors exhibited a reduced vascular density, which induced the expression of oxidative stress signaling pathways and increased levels of tissue hypoxia and necrosis. These alterations were paralleled by the suppression of genes involved in chromosomal stability and key effectors of the ATM-dependent/ non-homologous end-joining pathways including phosphorylated-ATM, BRCA1, and RAD51, which resulted in greater DNA double-strand breaks and caspase 3 activation following IR treatment. Conclusions/ Significance: Taken together, these results demonstrate that disruption of TNFα signaling in the host stroma mediates transcriptional and phenotypic changes in tumors which may alter tumor radiosensitivity. These results suggest a critical role for TNFα in the maintenance of tumor-associated vasculature and radioresistance. They also indicate that TNFα signaling blockade in stromal cells may represent a strategy for tumor radiosensitization. To investigate the genes associated with the radiosensitization of B16F1 melanoma tumors in the context of disrupted stromal TNFα signaling, we performed expression profiling of B16F1 tumors grown in syngeneic TNFR 1, 2 -/- and wild-type C57BL/6 mice. Tumors were lysed to collect total RNA, pooled by treatment group according to total RNA level, and analyzed in duplicates with Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays.

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Effects of tenascin-C on gene expression in mouse mammary gland tumor

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