Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes.
We investigated the influence of normal cell phenotype on the neoplastic phenotype by comparing tumors derived from two different normal human mammary epithelial cell populations, one of which was isolated using a new culture medium. Transformation of these two cell populations with the same set of genetic elements yielded cells that formed tumor xenografts exhibiting major differences in histopathology, tumorigenicity, and metastatic behavior. While one cell type (HMECs) yielded squamous cell carcinomas, the other cell type (BPECs) yielded tumors closely resembling human breast adenocarcinomas. Transformed BPECs gave rise to lung metastases and were up to 10(4)-fold more tumorigenic than transformed HMECs, which are nonmetastatic. Hence, the pre-existing differences between BPECs and HMECs strongly influence the phenotypes of their transformed derivatives.
Ince
Tan A
TA
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Richardson
Andrea L
AL
Bell
George W
GW
Saitoh
Maki
M
Godar
Samuel
S
Karnoub
Antoine E
AE
Iglehart
James D
JD
Weinberg
Robert A
RA
D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology; D000328:Adult; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D014183:Transplantation, Heterologous
D000952:Antigens, Polyomavirus Transforming; D014408:Biomarkers, Tumor