Overexpression of bamacan/SMC3 causes transformation

Bamacan can occur in certain cell types as either a secreted proteoglycan a ssembled into basement membranes or as an intracellular protein known as st ructural maintenance of chromosome 3 (SMC3). To assess the role of this pro tein in tumorigenesis, we investigated whether induced overexpression of ba macan/SMC3 could transform normal fibroblasts. We generated a full-length c DNA encoding the entire mouse bamacan/SMC3 and demonstrated appropriate tra nscription and translation into a 146-kDa protein. AU the NIH and Balb/c 3T 3 murine fibroblasts overexpressing this bamacan/SMC3 transgene generated f oci of transformation and acquired anchorage-independent growth. The increa sed levels of bamacan/SMC3 expression achieved in the transfected fibroblas ts were the same as those detected in a series of spontaneously transformed murine and human colon carcinoma cells. Moreover, a 3-4-fold overexpressio n of bamacan/SMC3 was detected in similar to 70% of human colon carcinoma s pecimens from matched pairs (n = 19, p < 0.0002) and in a cohort of intesti nal tumors from Apc-deficient Min/+ mice. These results support the concept that deregulated expression of bamacan/SMC3 is involved in cell transforma tion.