Sb. Ratsch et al., Multiple genetic changes are required for efficient immortalization of different subtypes of normal human mammary epithelial cells, RADIAT RES, 155(1), 2001, pp. 143-150
Breast cancer is the second leading cause of cancer-related deaths of women
in the U.S. About 180,000 new cases of breast cancer are diagnosed each ye
ar, a quarter of them fatal. Early detection is the key to the survival of
these patients. However, there are no molecular markers to detect breast ca
ncer at very early stages. A hurdle in understanding the early molecular ch
anges in breast cancer has been the difficulty in establishing premalignant
lesions and primary breast tumors as in vitro cell cultures. Normal epithe
lial cells grow for a finite life span and then senesce. Immortalization is
defined by continuous growth of otherwise senescing cells and is believed
to represent an early stage in tumor progression, To examine these early st
ages, we and others have developed in vitro models of mammary epithelial ce
ll immortalization. These models have been extremely important in understan
ding the role of various tumor suppressor pathways that maintain the normal
phenotypes of mammary epithelial cells. In this paper, we describe the est
ablishment of these models and their relevance to understanding the molecul
ar changes that occur in early breast cancer. These models have helped to i
dentify molecular changes that occur in early breast cancers and appear to
be well suited to identify novel markers for early diagnosis of breast canc
er. (C) 2001 by Radiation Research Society.