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

CDC37 encodes a 50-kDa protein that targets intrinsically unstable oncoprot ein kinases including Cdk4, Raf-1, and v-src to the molecular chaperone Hsp 90, an interaction that is thought to be important for the establishment of signaling pathways. CDC37 is required for proliferation in budding yeast a nd is coexpressed with cyclin D1 in proliferative zones during mouse develo pment, a finding consistent with a positive role in cell proliferation. CDC 37 expression may not only be required to support proliferation in cells th at are developmentally programmed to proliferate but may also be required i n cells that are inappropriately induced to initiate proliferation by oncog enes. Here we report that mouse mammary tumor virus (MMTV)-CDC37 transgenic mice develop mammary gland tumors at a rate comparable to that observed pr eviously in MMTV-cyclin D1 mice. Moreover, CDC37 was found to collaborate w ith 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 t hat CDC37 can function as an oncogene in mice and suggests that the establi shment of protein kinase pathways mediated by Cdc37-Hsp90 can be a rate-lim iting event in epithelial cell transformation.