Premium
Increased expression of MDM2, cyclin D1, and p27 Kip1 in carcinogen‐induced rat mammary tumors
Author(s) -
Murray Stephen A.,
Yang Shi,
Demicco Elizabeth,
Ying Haoqiang,
Sherr David H.,
Hafer Laurie J.,
Rogers Adrianne E.,
Sonenshein Gail E.,
Xiao ZhiXiong Jim
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20414
Subject(s) - dmba , carcinogenesis , cyclin d1 , carcinogen , cancer research , immunohistochemistry , protein kinase b , biology , 7,12 dimethylbenz[a]anthracene , mammary gland , cyclin d , western blot , mammary tumor , pi3k/akt/mtor pathway , chemistry , cell cycle , cancer , breast cancer , signal transduction , microbiology and biotechnology , biochemistry , immunology , genetics , gene
It is thought that environmental pollutants, such as polycyclic aromatic hydrocarbons (PAH), contribute to human breast tumorigenesis, yet their roles remain incompletely elucidated. The prototypical PAH 7,12‐dimethylbenz(α)anthracene (DMBA) specifically and effectively induces mammary tumor formation in rodent models. In an attempt to explore the molecular mechanisms by which PAH initiates and promotes mammary tumorigenesis, we examined the expression of several cell cycle regulators in rat mammary tumors induced by DMBA. Expression of cyclin D1, murine double minute‐2 (MDM2), and Akt was up‐regulated in tumors in comparison to normal mammary glands, as indicated by RT‐PCR, Western blot analysis, and immunohistochemical staining. Expression of p27 Kip1 protein was also elevated in the tumors with increased cytoplasmic localization. However, RB protein remained hyperphosphorylated. To directly test the effects of DMBA, the MCF‐7 human breast cancer cells were treated. DMBA induced MDM2 expression in a dose‐ and time‐dependent fashion in the MCF‐7 cells, and this activation appeared to be p53 dependent. These data suggest that activation of cyclin D1, MDM2, and AKT as well as increased expression and cytoplasmic localization of p27 Kip1 may play a role in this model of environmental pollutant‐induced mammary tumorigenesis. © 2005 Wiley‐Liss, Inc.