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

The Cdc37 gene encodes a 50 kDa protein which targets intrinsically unstabl e oncoprotein kinases such as Cdk4, Raf-1, and src to the molecular chapero ne Hsp90, This activity is thought to play an important role in the establi shment of signaling pathways controlling proliferation. The budding yeast C dc37 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 inc reased Cdc37 expression, suggesting an important and early role for Cdc37 i n prostatic transformation. To test the consequences of increased Cdc37 lev els, transgenic mice expressing Cdc37 in the prostate were generated, These mice displayed a wide range of growth-related abnormalities including pros tatic epithelial cell hyperplasia and dysplasia. These data suggest that th e expression of Cdc37 may promote inappropriate proliferation and may be an important early step in the development of human prostate cancer.