Expression of CDK inhibitor genes in immortalized and carcinoma derived breast cell lines.

The expression of the CDK inhibitor (CDI) genes p15(INK4B), p16(INK4A), p18 and p21Cip1 was examined in immortalized, non-tumorigenic cell lines derived from human breast epithelium, and in breast carcinoma derived lines. An increase in p16 expression, suggesting loss of pRb function, was recorded in two immortalized lines, and complete absence of p16 mRNA was observed in the third. In contrast, high levels of p21Cip1 mRNA were found in two immortalized lines. In addition to differences in p16 and p21Cipl, variations in the expression of p15 and p18 mRNA were observed between different cell lines. Immortalized A1N4 and HBL100 cells, as well as ER+, MCF-7 carcinoma cells, expressed high levels of p15 mRNA. A1N4, HBL100 cells and highly malignant ER MDA-MB-231 cells expressed high levels of p18 mRNA. Inhibition by genistein indicated that p18 mRNA expression was dependent on cellular tyrosine kinases in these cells. We conclude that the pattern of p15 and p18 mRNA expression was distinct from that of p16 and p21Cip1, suggesting different modes of regulation.