Induction of human Cdc37 in prostate cancer correlates with the ability of targeted Cdc37 expression to promote prostatic hyperplasia.
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.
Stepanova
L
L
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Yang
G
G
DeMayo
F
F
Wheeler
T M
TM
Finegold
M
M
Thompson
T C
TC
Harper
J W
JW
D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D018833:Chaperonins; D029721:Drosophila Proteins; D004848:Epithelium / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000209:etiology*; D011994:Recombinant Proteins / Q000096:biosynthesis
C498362:CDC37 protein, human; C513271:Cdc37 protein, mouse; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D018833:Chaperonins