title: A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis.
abstract: Two types of human breast epithelial cells (HBEC) have been characterized. In contrast to Type II HBEC, which express basal epithelial cell phenotypes, Type I HBEC are deficient in gap junctional intercellular communication and are capable of anchorage-independent growth and of expressing luminal epithelial cell markers, estrogen receptors, and stem cell characteristics (i.e. the ability to differentiate into other cell types and to form budding/ductal organoids on Matrigel). A comparative study of these two types of cells has revealed a high susceptibility of Type I HBEC to immortalization by SV40 large T antigen, although both types of cells are equally capable of acquiring an extended life span (bypassing senescence) after transfection with SV40. The immortalization was accompanied by elevation of a low level of telomerase activity in the parental cells after mid-passage ( approximately 60 cumulative population doubling levels). Thus HBEC do have a low level of telomerase activity, and Type I HBEC with stem cell characteristics are more susceptible to telomerase activation and immortalization, a mechanism which might qualify them as target cells for breast carcinogenesis. The immortalized Type I HBEC can be converted to highly tumorigenic cells by further treatment with X rays (2 Gy x 2) and transfection with a mutated ERBB2 (also known as NEU) oncogene, resulting in the expression of p185(ERBB2) which is tyrosine phosphorylated.
authors: National Food Safety and Toxicology Center, Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan 48824, USA.
authors: C C
authors: CC
authors: Chang
authors: W
authors: W
authors: Sun
authors: A
authors: A
authors: Cruz
authors: M
authors: M
authors: Saitoh
authors: M H
authors: MH
authors: Tai
authors: J E
authors: JE
authors: Trosko
mesh_terms: D000818:Animals; D001940:Breast / Q000166:cytology* / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D006801:Humans; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology; D019098:Telomerase / Q000378:metabolism
chemical_list: D019098:Telomerase