Bone morphogenetic protein 2 (BMP-2) induces sequential changes of Id geneexpression in the breast cancer cell line MCF-7

Bone morphogenetic proteins (BMPs) are involved in the development of vario us organs including the mammary gland. They are well-regulated and act in a time-, concentration- and cell-type-specific manner. We found that BMP-2 i s expressed in primary breast tumor tissue samples and in breast cancer cel l lines. Hybridization of labeled cDNA, obtained from the breast cancer cel l line MCF-7, against the Atlas human cDNA expression array revealed differ ential gene expression depending on BMP-2 treatment. The most prominent cha nges were observed for the helix-loop-helix proteins Id-1, Id-2 and Id-3. I d-1 expression had increased severalfold after 4 h and was even higher afte r 24 h. Id-2 and Id-3 were more strongly induced after 4 h and showed no fu rther significant change after 24 h. Analysis of cell-cycle distribution re vealed a marked increase of the sub-G1 phase after 48 h in serum-deprived c ells. III the presence of BMP-2 no change was observed over 48 h indicating that BMP-2 does not induce apoptosis. In addition, expression of caspase-3 was reduced in BMP-2-treated cells after 24 h. In summary, our results cle arly indicate that BMP-2 is a susceptibility factor keeping the cells ready for the integration of various other signals for cell progression.