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Induction of human Cdc37 in prostate cancer correlates with the ability of targeted Cdc37 expression to promote prostatic hyperplasia

Oncogene volume 19, pages 2186–2193 (2000)Cite this article

Abstract

The Cdc37 gene encodes a 50 kDa protein which targets intrinsically unstable oncoprotein kinases such as Cdk4, Raf-1, and src to the molecular chaperone Hsp90. This activity is thought to play an important role in the establishment of signaling pathways controlling cell proliferation. The budding yeast Cdc37 homolog is required for cell division and mammalian Cdc37 is expressed in proliferative zones during embryonic development and in adult tissues, consistent with a positive role in proliferation. Here we report that human prostatic tumors, neoplasias and certain pre-malignant lesions display increased Cdc37 expression, suggesting an important and early role for Cdc37 in prostatic transformation. To test the consequences of increased Cdc37 levels, transgenic mice expressing Cdc37 in the prostate were generated. These mice displayed a wide range of growth-related abnormalities including prostatic epithelial cell hyperplasia and dysplasia. These data suggest that the expression of Cdc37 may promote inappropriate proliferation and may be an important early step in the development of human prostate cancer.

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Acknowledgements

We thank Norman Greenberg for access to microscope facilities. This work was supported by grants from the NIH (GM54137) and the Welch Foundation to JW Harper, and by the Baylor SPORE in Prostate Cancer (NCI P50-58204) to TC Thompson. L Stepanova is supported by a Pre-Doctoral training grant from the Department of Defense.

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Author notes

  1. Lilia Stepanova

    Present address: Department of Tumor Cell Biology, St. Judes Children's Research Hospital, Memphis, 38105, Tennessee, TN, USA

Authors and Affiliations

  1. Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, TX, USA

    Lilia Stepanova & J Wade Harper

  2. Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, TX, USA

    Thomas M Wheeler & Milton Finegold

  3. Scott Department of Urology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, TX, USA

    Guang Yang & Timothy C Thompson

  4. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, TX, USA

    Franco DeMayo & Timothy C Thompson

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Stepanova, L., Yang, G., DeMayo, F. et al. Induction of human Cdc37 in prostate cancer correlates with the ability of targeted Cdc37 expression to promote prostatic hyperplasia. Oncogene 19, 2186–2193 (2000). https://doi.org/10.1038/sj.onc.1203561

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