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Originally published In Press as doi:10.1074/jbc.C000213200 on May 3, 2000

J. Biol. Chem., Vol. 275, Issue 27, 20235-20238, July 7, 2000
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ACCELERATED PUBLICATION
Overexpression of Bamacan/SMC3 Causes Transformation*

Giancarlo GhiselliDagger and Renato V. IozzoDagger §

From the Dagger  Department of Pathology, Anatomy and Cell Biology, and § Program in Cell Biology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Bamacan can occur in certain cell types as either a secreted proteoglycan assembled into basement membranes or as an intracellular protein known as structural maintenance of chromosome 3 (SMC3). To assess the role of this protein in tumorigenesis, we investigated whether induced overexpression of bamacan/SMC3 could transform normal fibroblasts. We generated a full-length cDNA encoding the entire mouse bamacan/SMC3 and demonstrated appropriate transcription and translation into a 146-kDa protein. All the NIH and Balb/c 3T3 murine fibroblasts overexpressing this bamacan/SMC3 transgene generated foci of transformation and acquired anchorage-independent growth. The increased levels of bamacan/SMC3 expression achieved in the transfected fibroblasts were the same as those detected in a series of spontaneously transformed murine and human colon carcinoma cells. Moreover, a 3-4-fold overexpression of bamacan/SMC3 was detected in ~70% of human colon carcinoma specimens from matched pairs (n = 19, p < 0.0002) and in a cohort of intestinal tumors from Apc-deficient Min/+ mice. These results support the concept that deregulated expression of bamacan/SMC3 is involved in cell transformation.

* This work was supported by National Institutes of Health Grants RO1 CA39481 and RO1 CA47282 (to R. V. I).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pathology, Anatomy and Cell Biology, Rm. 249, JAH, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA 19107. E-mail: iozzo@lac.jci. tju.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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