Open AccessIncreased Expression of Cyclin D1, Cyclin E and p21 Cip1 Associated with Decreased Expression of p27 Kip1 in Chemically Induced Rat Mammary Carcinogenesis
Author(s) -
Jang Tae Jung,
Kang Myung Soo,
Kim Heesoo,
Kim Dong Hoon,
Lee Jong Im,
Kim Jung Ran
Publication year - 2000
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2000.tb00908.x
Subject(s) - cyclin d1 , mammary gland , immunohistochemistry , biology , cyclin , cyclin d , 7,12 dimethylbenz[a]anthracene , carcinogenesis , dmba , cyclin e , cyclin a , cancer research , cyclin b , cell cycle , endocrinology , pathology , medicine , cancer , breast cancer , immunology , genetics
We induced rat mammary tumors in 7‐week‐old female Sprague‐Dawley rats by intragastric administration of 7,12‐dimethylbenz( a )anthracene (DMBA), and analyzed by immunohistochemistry the expression of cyclin D1, cyclin E, p21 Cip1 , and p27 Kip1 in carcinomas, atypical tumors, and benign tumors as well as normal mammary glands from the control group. Proliferation status was assessed by immunohistochemistry using bromodeoxyuridine (BrdU). A sequential increase in cyclin D1‐, cyclin E‐, and p21 Cip1 ‐positive epithelial cells was observed from normal mammary glands, to atypical tumors, to carcinomas. In contrast, carcinomas showed a significantly lower number of epithelial cells immunoreactive to p27 Kip1 when compared with atypical tumors, benign tumors and normal mammary glands. The immunoreactivities of BrdU, cyclin D1, cyclin E, and p21 Cip1 were positively correlated, whereas that of p27 Kip1 appeared inversely correlated to those of the others. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and western blot analysis were also performed to determine the mRNA and protein levels of cyclins and cyclin‐dependent kinase inhibitors in tumors and normal mammary glands. The protein levels for cyclin D1, cyclin E and p21 Cip1 in carcinomas and atypical tumors were significantly higher than those in benign tumors, while normal mammary glands showed negligible expression. On RT‐PCR, tumors showed higher mRNA levels of cyclin D1 and cyclin E than those of normal mammary glands. Our results suggest that rat mammary carcinogenesis involves increased expression of cyclin D1, cyclin E, and p21 Cip1 , associated with decreased expression of p27 Kip1