CORRELATION BETWEEN CELL-CYCLE REGULATORS AND THE IMMORTALIZATION ANDTRANSFORMATION OF HUMAN BREAST EPITHELIAL-CELL LINES

Cellular proliferation, essential for normal development, may result i n neoplastic growth when the cell cycle clock is disrupted. In order t o determine whether the protein expression of cell cycle regulators di ffers among normal, immortalized non-tumorigenic and malignant human b reast epithelial cells (HBECs), we analyzed the protein expression of cyclins D1, D3, A and E, cyclin-dependent kinase (cdk) 4 and c-fos in exponentially growing MCF-10M, MCF-10F, and MCF-7 cells. The tumorigen icity of HBECs in vivo correlated with both cell cycle regulators and early-gene protein expression in vitro. The differential expression of cyclin E- and cyclin A-related proteins and their putative relevance in the tumorigenic properties of HBECs are also discussed.