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Molecular and Cellular Biology, June 2000, p. 4462-4473, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Oncoprotein Kinase Chaperone CDC37 Functions as an Oncogene in Mice and Collaborates with Both c-myc and Cyclin D1 in Transformation of Multiple Tissues

Lilia Stepanova,1,dagger Milton Finegold,2 Franco DeMayo,3 Emmett V. Schmidt,4 and J. Wade Harper1,*

Verna and Marrs McLean Department of Biochemistry and Molecular Biology,1 Department of Pathology,2 and Department of Molecular and Cellular Biology,3 Baylor College of Medicine, Houston, Texas 77030, and The MGH Cancer Center, Department of Tumor Biology, Charlestown, Massachusetts 021294

Received 5 November 1999/Returned for modification 28 December 1999/Accepted 15 March 2000

CDC37 encodes a 50-kDa protein that targets intrinsically unstable oncoprotein kinases including Cdk4, Raf-1, and v-src to the molecular chaperone Hsp90, an interaction that is thought to be important for the establishment of signaling pathways. CDC37 is required for proliferation in budding yeast and is coexpressed with cyclin D1 in proliferative zones during mouse development, a finding consistent with a positive role in cell proliferation. CDC37 expression may not only be required to support proliferation in cells that are developmentally programmed to proliferate but may also be required in cells that are inappropriately induced to initiate proliferation by oncogenes. Here we report that mouse mammary tumor virus (MMTV)-CDC37 transgenic mice develop mammary gland tumors at a rate comparable to that observed previously in MMTV-cyclin D1 mice. Moreover, CDC37 was found to collaborate with MMTV-c-myc in the transformation of multiple tissues, including mammary and salivary glands in females and testis in males, and also collaborates with cyclin D1 to transform the female mammary gland. These data indicate that CDC37 can function as an oncogene in mice and suggests that the establishment of protein kinase pathways mediated by Cdc37-Hsp90 can be a rate-limiting event in epithelial cell transformation.

* Corresponding author. Mailing address: Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6993. Fax: (713) 796-9438. E-mail: jharper{at}bcm.tmc.edu.

dagger Present address: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105.

Molecular and Cellular Biology, June 2000, p. 4462-4473, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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