CORRELATION OF CD44 EXPRESSION WITH PROLIFERATIVE ACTIVITY OF NORMAL HUMAN BREAST EPITHELIAL-CELLS IN CULTURE

A number of studies have shown that certain variant isoforms of CD44 a re overexpressed in human breast cancer, suggesting their use as indic ators of the presence of malignant cells. We now show that CD44 isofor m mRNA and protein expression is upregulated in normal human breast ep ithelial cells (HBEC) when these cells are stimulated to proliferate i n culture. Reverse transcription-PCR analysis of cultured normal HBEC revealed complex patterns of CD44 mRNA expression that were indistingu ishable from patterns previously shown to be characteristic of tissue samples containing malignant HBEC. CD44v6-expressing cells were identi fied in cultures generated from FAGS-purified populations of either no rmal luminal (CALLA(-)MUC-1(+)) or myoepithelial (CALLA(+)MUC-1(-)) ce lls, even though immunohistochemical analysis of normal breast tissue sections confirmed CD44v6 expression to be limited to the myoepitheliu m in vivo. Increased expression of both CD44v mRNA and protein in cult ured populations of normal HBEC was shown to correlate positively with the proportion of cells that were proliferating (Ki-67(+)) independen t of cell density. These results indicate that activation of CD44 vari ant isoform expression in HBEC occurs as a normal response to factors that stimulate their proliferation and suggests caution in the use of this marker to identify malignant cells.