Genetically determined inflammatory-response related cytokine and chemokine transcript profiles between mammary carcinoma resistant and susceptible rat strains

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2012-08, Vol.59 (2), p.223-227
• Main Authors: Devapatla, Bharat, Sanders, Jennifer, Samuelson, David J.
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; alleles; Analysis of Variance; Animals; anthracenes; Breast cancer susceptibility; carcinogenesis; carcinoma; Ccl20; chemokines; Chemokines - genetics; Cxcr7; Female; females; Gene Expression Profiling; gene expression regulation; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; genotype; Humans; immune system; Inflammation; Inflammation - genetics; interleukin-4; mammary glands; Mammary Neoplasms, Experimental - genetics; messenger RNA; Rat mammary carcinogenesis; Rats; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2012.04.037

► We compared inflammatory genes in a rat genetic model of human breast cancer. ► Most differentially expressed transcripts were higher in resistant mammary glands. ► Transcripts different in carcinogen exposed/unexposed females were identified. ► Mammary Cxcr7 was higher relative to Cxcr4 in carcinogen exposed resistant females. Multiple human breast and rat mammary carcinoma susceptibility (Mcs) alleles have been identified. Wistar Kyoto (WKY) rats are resistant to developing mammary carcinomas, while Wistar Furth (WF) females are susceptible. Gene transcripts at Mcs5a1, Mcs5a2, and Mcs5c are differentially expressed between resistant WKY and susceptible WF alleles in immune-system tissues. We hypothesized that immune-related gene transcript profiles are genetically determined in mammary carcinoma resistant and susceptible mammary glands. Low-density QPCR arrays were used to compare inflammation related genes between mammary carcinoma resistant WKY and susceptible WF females. Mammary gland gene transcript levels predicted to be different based on arrays were tested in independent samples. In total, 20 females per strain were exposed to 7,12-dimethylbenz(a)anthracene (DMBA) to induce mammary carcinogenesis. Twelve age-matched controls per strain without DMBA were included to determine main effects of DMBA-exposure. Significant (ANOVA P⩽0.01) effects of strain on mammary gland transcript level were observed for Cx3cl1, Il11ra, Il4, C3, Ccl20, Ccl11, Itgb2, Cxcl12, and Cxcr7. Significant effects of DMBA-exposure were observed for Cx3cl1, Il11ra, Cxcr4, Il4ra, and Il4. Strain and DMBA-exposure interaction effects were significant for Cx3cl1. Transcript levels of Cxcr7 relative to Cxcr4 were modified differently by DMBA in mammary carcinoma resistant and susceptible strains. In conclusion, several genetically-determined differences in cytokine, chemokine, and receptor gene transcript levels were identified between mammary carcinoma susceptible and resistant mammary glands, which may be indicative of cell populations and activities that suppress mammary carcinogenesis in resistant genotypes.