Oncogenic signaling pathways activated in DMBA-induced mouse mammary tumors
| Autor: | Elizabeth G. Demicco, Zhi-Xiong Jim Xiao, Gail E. Sonenshein, Haoqiang Ying, Nicolas Currier, Sandra E. Solomon, Robert D. Cardiff, Isabel Dominguez, Marganit Farago, David H. Sherr, Donny L.F. Chang, David C. Seldin |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
040301 veterinary sciences 9 10-Dimethyl-1 2-benzanthracene Mammary gland Genes myc DMBA Apoptosis Toxicology medicine.disease_cause 030226 pharmacology & pharmacy Retinoblastoma Protein Pathology and Forensic Medicine 0403 veterinary science 03 medical and health sciences Mice 0302 clinical medicine Cyclin D1 Internal medicine medicine Animals RNA Messenger Casein Kinase II Molecular Biology Carcinogen beta Catenin biology Retinoblastoma Wnt signaling pathway NF-kappa B Mammary Neoplasms Experimental 04 agricultural and veterinary sciences Cell Biology DNA Oncogenes Peptidylprolyl Isomerase Aryl hydrocarbon receptor medicine.disease Genes bcl-1 Gene Expression Regulation Neoplastic NIMA-Interacting Peptidylprolyl Isomerase Wnt Proteins medicine.anatomical_structure Endocrinology Receptors Aryl Hydrocarbon biology.protein Carcinogens Female Carcinogenesis Signal Transduction |
| Zdroj: | Toxicologic pathology. 33(6) |
| ISSN: | 0192-6233 |
| Popis: | Only about 5% of human breast cancers can be attributed to inheritance of breast cancer susceptibility genes, while the balance are considered to be sporadic in origin. Breast cancer incidence varies with diet and other environmental influences, including carcinogen exposure. However, the effects of environmental carcinogens on cell growth control pathways are poorly understood. Here we have examined oncogenic signaling pathways that are activated in mammary tumors in mice treated with the prototypical polycyclic aromatic hydrocarbon (PAH) 7,12-dimethylbenz[ a]anthracene (DMBA). In female FVB mice given 6 doses of 1 mg of DMBA by weekly gavage beginning at 5 weeks of age, all of the mice developed tumors by 34 weeks of age (median 20 weeks after beginning DMBA); 75% of the mice had mammary tumors. DMBA-induced mammary tumors exhibited elevated expression of the aryl hydrocarbon receptor (AhR), c- myc, cyclin D1, and hyperphosphorylated retinoblastoma (Rb) protein. Because of this, the activation of upstream regulatory pathways was assessed, and elements of the Wnt signaling pathway, the NF-κB pathway, and the prolyl isomerase Pin-1 were found to be frequently up-regulated in the tumors when compared to normal mammary gland controls. These data suggest that environmental carcinogens can produce long-lasting alterations in growth and anti-apoptotic pathways, leading to mammary tumorigenesis. |
| Databáze: | OpenAIRE |
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