Characterization of an In Vitro Human Breast Epithelial Organoid System
Annual rept. 1 Aug 1998-31 Jul 1999,
MICHIGAN STATE UNIV EAST LANSING
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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.
- Anatomy and Physiology
- Medicine and Medical Research