The pathway of neoplastic transformation of human breast epithelial cells

The morphological analysis of breast cancer development indicates this to b e a multistep process that progressively evolves from ductal hyperplasia an d atypical ductal hyperplasia, which represent the initial stages of neopla stic growth, to carcinoma in situ, invasive carcinoma, and ultimately metas tasis, as has been documented for a number of other malignancies, The under standing of the cellular and molecular processes that lead a normal cell to malignancy requires the analysis of pure populations of human breast epith elial cells (HBEC) representing specific stages of neoplastic progression. The neoplastic transformation of HBEC in vitro represents a successful mode l for obtaining knowledge about the molecular and biological alterations th at may contribute to the tumorigenic mechanisms. We present here a current understanding of chemically transformed HBEC in the following aspects: (1) factors affecting the transformation of HBEC such as immortalization; (2) n ew targets for studying the mechanism of cell immortalization such as alter ations in telomerase activity, differential expression of cell cycle-depend ent genes, and others recently isolated through differential cloning, such as H-ferritin, and a calcium binding protein; (3) genetic mechanisms underl ying cell transformation; and (4) application of the microcell-mediated chr omosome transfer technique as an approach to testing the functional role of specific genes whose dysregulation or loss of function may contribute to t he ultimate cell transformation. Further efforts in this cell system will b e directed to determining the roles of identified molecular changes as well as the mapping/cloning of tumor suppressor or senescence genes. (C) 2001 b y Radiation Research Society.