An in vitro model of human breast carcinogenesis: epigenetic aspects.

A review is given of 12 years of research on a human breast epithelial cell line, HMT-3522, which has undergone malignant transformation in vitro without being exposed to known carcinogenic agents. Epigenetic aspects of the malignant transformation have been considered and the results have been viewed in a clinical context. It has been concluded that the history and characteristics of the cell line resembles the comedocarcinoma of the human breast. It is hypothesized that progression from benign lesion to comedo in situ carcinoma and invasive carcinoma occurs if low levels of epidermal growth factor are prevailing in the microenvironment. Our data also suggest that breast cancer developed under high epidermal growth factor receptor activity is estrogen receptor negative, while suppression of epidermal growth factor receptor activity promotes estrogen responsive breast cancer.