Characterization of an In Vitro Human Breast Epithelial Organoid System
Final rept. 1 Aug 1996-31 Jul 2001
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 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.
- Medicine and Medical Research