In Vitro Models of Early Neoplastic Transformation of Human Mammary Epithelial Cells

About 80% of all human cancers are carcinomas, representing oncogenic transformation of epithelial cells. In-vitro models of epithelial cell transformation are therefore of great interest to elucidate the molecular mechanisms of human cancer. Malignant transformation is a multistep process in which genetic changes and environmental factors, including viruses, carcinogens, radiation, and dietary factors, impinge on common cellular pathways resulting in uncontrolled proliferation, a hallmark of tumorigenic process (1 ,2 ). Understanding the nature of these cellular pathways is a central goal in cancer biology. A critical event in oncogenesis is the conversion of normal epithelial cells with a finite proliferative potential into cells endowed with an ability to multiply continuously, a trait that allows the accumulation of further genetic alterations resulting in full malignancy. In vitro, this behavior manifests as continuous proliferation of cells beyond their limited life span, a process referred to as immortalization. Understanding the biochemical basis of immortalization is therefore likely to point to crucial tumor suppressor pathways that ensure the untransformed state of normal epithelial cells.