G₁ Cell Cycle Regulatory Proteins in Chemically-Induced Rat Mammary Adenocarcinomas In Vivo and Tumor Promotion-Sensitive, -Resistant and Transformed Mouse Epidermal Cells In Vitro

Abstract

Tumor promotion is characterized by selective proliferation of initiated cells resulting in their clonal expansion. Cyclin D1 is frequently upregulated in this process, but its expression does not necessarily correlate positively with cyclin A. In the present article, expression of G₁ cell cycle regulatory proteins was systematically analyzed using two models of carcinogenesis: (a) N-methyl-N-nitrosourea (MNU)-induced rat mammary adenocarcinomas and normal rat mammary epithelial cells in vivo and (b) promotion- sensitive, -resistant, and transformed JB6 mouse epidermal cells in vitro. The results of this analysis revealed that p27Kip1 negatively correlated with cyclin D1. In addition, there were two types of correlations between p27Kip1 and cyclin A. First, p27Kip1 negatively correlated with cyclin A (type-I correlation). This scenario was observed in normal rat mammary epithelial cells in vivo and promotion-sensitive (P+) JB6 mouse epidermal cells, stimulated with phorbol ester (TPA) in vitro. Second, p27Kip1 positively correlated with cyclin A (type-II correlation). This correlation was observed in MNU-induced rat mammary adenocarcinomas in vivo and TPA-stimulated (P+) JB6 cells, treated with retinoic acid in vitro.