Cultured human breast carcinoma cell lines are important models for investi
gating the pathogenesis of breast cancer. Their use, however, is limited be
cause of loss of expression of breast-specific markers and the development
of a dedifferentiated phenotype after continuous culture. PMC42 is a unique
human breast carcinoma line, previously shown to express secretory and myo
epithelial markers. We have induced PMC42 cells to form hollow organoids in
culture, similar to in vivo breast structures, using a combination of horm
ones including estrogen, progesterone, dexamethasone, insulin, and prolacti
n in combination with a permeable extracellular matrix. The organoids compr
ised polarized cells located around a central lumen. Expression of beta -ca
sein was demonstrated in cells within organoids using reverse transcriptase
-polymerase chain reaction, Western blot analysis, and confocal immunofluor
escence, In this in vitro system, milk-specific gene expression was induced
through hormone and matrix interactions which may be similar to those oper
ating in vivo, PMC42 is a novel model for investigations into the molecular
mechanisms of carcinogenesis and differentiation in the human breast. (C)
2001 Academic Press.