Breast carcinoma is one of the most common malignant
tumors and has become a more common
cancer in women. BMP6 was abnormally expressed in
breast cancer specimens and cell lines. However, the contribution of BMP6 in promoting
breast cancer progression remains unknown. The purpose of our study was to establish whether expression of BMP6 in
breast cancer cells affect their proliferation or apoptosis and the mechanism. We found that BMP6 inhibited proliferation of MDA-MB-231 cells and blocked cell cycle at G(0)/G(1) stage. BMP6 also inhibited serum deprivation induced apoptosis in MDA-MB-231 cells. At the 4 days of serum
starvation, BMP6 reduced the percentage of
caspase-3 positive cells from 49% to 21%, BMP6 also reduced sub-G(1) peak induced by serum
starvation. In contrast, BMP6 significantly enhanced
survivin expression both at
mRNA and
protein levels. Dominant negative-
survivin and Antisense-
survivin impaired BMP6 induced antiapoptotic effect. BMP6 enhanced
survivin expression at the transcription level in a Smad-dependent manner. BMP6 also played its antiapoptotic effect through activation
p38 MAPK signal pathway, independent of smad/
survivin pathway. These results suggested that BMP6 induced cell cycle arrest in
estrogen-insensitive
breast cancer cells. BMP6 inhibits stress-induced apoptosis via both Smad and p38 signal pathways.