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 or lobule 1-like structures in Matrigel which preserve the undifferentiated state of HBEC for a long time, evidence that Type I HBEC are stem cells; (2) Type I normal HBEC and their neoplastically transformed clones express a variant ER-A in vitro on plastic while expressing a wild type ER-A in tumors developed in nude mice or grown in vitro in Matrigel (3) The -46kd variant ER-A is the result of splicing deletion of exon 1 in ER-A transcript; Type I HBEC use promoter A while immortal and tumorigenic Type I cells use both promoter A and C for transcription; and (4) high susceptibility of Type I HBEC to telomerase activation and immortalization,, a basis on which Type I EBEC (stem cells) are major targets for carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA399831
Entities
People
- Chia-cheng Chang
Organizations
- Michigan State University