Glypican-3 expression is silenced in human breast cancer

Glypican-3 (GPC3) is, a membrane-bound heparan sulfate proteoglycan that is mutated in the Simpson-Golabi-Behmel syndrome. This is an X-linked conditi on characterized by overgrowth, and various visceral and skeletal dysmorphi sms. The phenotype of the Simpson-Golabi-Behmel, syndrome patients and GM-d eficient mice, as well as gene transfection experiments indicate that GPC3 can act as an inhibitor of cell proliferation and survival. It has been pre viously shown that GPC3 expression is downregulated in mesotheliomas and ov arian cancer. Here we report that GPC3 expression is also silenced in human . breast cancer, and that this silencing is due, at least in part, to hyper methylation of the GPC3 promoter. Ectopic expression of GPC3 inhibited grow th in eight out of 10 breast cancer cell lines. Collectively, these data su ggest that GPC3 can act as a negative regulator of breast cancer growth.