Characterization of an In Vitro Human Breast Epithelial Organoid System
Abstract
The objectives of this study are: (1) to identify factors that regulate the growth and differentiation of organoids formed by two types of normal human breast epithelial cells (HBEC) in Matrigel; (2) to characterize the expression and function of estrogen receptors (ER) in normal and in vitro neoplastically transformed HBEC; and (3) to determine if a HBEC type with stem cell characteristics (Type I) is more susceptible to telomerase activation and immortalization. The major results are: (1) Type I HBEC in conjunction with Type II cells are capable of forming ductal and end bud-like structures in Matrigel which preserve the undifferentiated state of HBEC for a long time; (2) Type I normal HBEC and their neoplastically transformed clones express a variant ER in vitro on plastic while expressing a wild type ER in tumors developed in nude mice or grown in vitro in Matrigel; (3) high susceptibility of Type I HBEC to telomerase activation and immortalization; and (4) the lifespan of HBEC can be effectively extended by co-transfection with a dominant-negative mutant p53 and the human c-myc. These findings indicate Type I stem cells as targets for carcinogenesis and inactivation of p53 and activation of telomerase as major events in initial stage of breast carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA378743
Entities
People
- Chia-cheng Chang
Organizations
- Michigan State University