title: Gene expression profiling in the mammary gland of rats treated with 7,12-dimethylbenz[a]anthracene.
abstract: Identification of molecular markers of early-stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real-time PCR, RT-PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of beta-casein and transferrin and higher expression of hsp27 in glands from DMBA-treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki-67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, alpha-tubulin and hsp27, were all overexpressed in the mammary gland of DMBA-treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development.
authors: Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Andriana D
authors: AD
authors: Papaconstantinou
authors: Ilanchezhian
authors: I
authors: Shanmugam
authors: Liang
authors: L
authors: Shan
authors: Insa S
authors: IS
authors: Schroeder
authors: Cunping
authors: C
authors: Qiu
authors: Minshu
authors: M
authors: Yu
authors: Elizabeth G
authors: EG
authors: Snyderwine
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000503:physiopathology*; D002273:Carcinogens / Q000633:toxicity*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000502:physiology*; D008870:Microtubules / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene