Journal Article

Gene expression profiling of chemically induced rat mammary gland cancer

Liang Shan, Minshu Yu and Elizabeth G. Snyderwine

in Carcinogenesis

Volume 26, issue 2, pages 503-509
Published in print February 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh330
Gene expression profiling of chemically induced rat mammary gland cancer

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Exposure to carcinogens through diet, the atmosphere and other means is generally regarded as influencing human cancer risk, but the impact of specific environmental carcinogens on human breast cancer incidence is still unknown. We examined whether distinct chemical carcinogens induce a unique transcriptional profile in mammary gland cancer that is characteristic of the etiologic agent. Rat mammary gland cancers (n = 34) were generated by various carcinogens, including the food-derived heterocyclic amines 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 7,12-dimethylbenz[a]anthracene, N-nitrosomethylurea and 4-aminobiphenyl. The histopathology of the carcinomas was graded using a modified Scarff-Bloom–Richardson scheme and the gene expression profiles in the carcinomas were evaluated on a 10K cDNA microarray. Unsupervised hierarchical clustering analysis revealed two major clusters of carcinomas irrespective of the carcinogenic agent that distinguished two groups with different histopathological parameters (degree of differentiation, nuclear grade, mitotic activity, epithelial cell growth pattern and necrosis). Using class comparison analysis and hierarchical clustering of all carcinomas irrespective of histopathology, gene expression profiles were further shown to be statistically differentially expressed according to the carcinogenic agent. These findings indicate that the transcriptional program in carcinomas is unique to the etiologic agent and can be observed among a diverse set of carcinogens despite variations in carcinoma histopathology. The ability to use microarray analysis to discern an etiology-specific profile among a pathologically heterogeneous group of breast carcinomas may ultimately be valuable in determining the role of environmental chemical carcinogens in human breast cancer risk.

Keywords: 4ABP, 4-aminobiphenyl; DMBA, 7,12-dimethylbenz[a]anthracene; MDS, multidimensional scaling; MelQx, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; NMU, N-nitrosomethylurea; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Journal Article.  4018 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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