Christine L. Hattrup¹,³, Judy M. Bradley, Kari L. Kotlarczyk, Cathy S. Madsen, Joseph G. Hentz, Ronald J. Marler² and Sandra J. Gendler¹

¹Department of Biochemistry and Molecular Biology, ²Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Mayo Clinic Arizona, 13400 E. Shea Boulevard, Scottsdale, Arizona, U.S.A. 85259, ³Current Address: Department of Laboratory Medicine, Mayo Clinic Rochester, 200 First Street SW, Rochester, Minnesota, 55905, U.S.A.

Abstract

Background: Though the importance of the transmembrane mucin MUC1 in mammary oncogenesis has long been recognized, the relative contributions of the cytoplasmic tail and tandem repeat domains are poorly understood.

Methods: To address this, mouse models of mammary carcinogenesis were created expressing full-length, cytoplasmic tail-deleted, or tandem repeat-deleted MUC1 constructs.

Results: Overexpression of full-length MUC1 resulted in tumor formation in young mice (12 months); however, loss of either the cytoplasmic tail or the tandem repeat domain abrogated this oncogenic capacity. Aged mice in all strains developed late-onset mammary tumors similar to those previously described for the FVB background.

Conclusions: This study is the fi rst spontaneous cancer model to address the relative importance of the cytoplasmic tail and tandem repeat domains to MUC1-driven mammary oncogenesis, and suggests that both of these domains are essential for tumor formation.

Discussion
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