Loss of 14-3-3sigma in prostate cancer and its precursors.
OBJECTIVE
The 14-3-3 family proteins are highly conserved over many mammalian species. The sigma isoform (also called HME-1 or stratifin) is expressed in epithelial cells. Loss of 14-3-3sigma is associated with failure to arrest the cell cycle at the G(2)-M phase checkpoint after DNA damage that leads to increased G(2)-type chromosomal aberrations. The role of 14-3-3sigma in prostatic carcinogenesis is uncertain.


METHODS
We studied one hundred and eleven specimens of invasive prostate adenocarcinoma with paired, adjacent high-grade prostatic intraepithelial neoplasia and normal prostate epithelium. Immunohistochemistry was used to detect the expression of 14-3-3sigma. The findings were correlated with various clinical pathological parameters.


RESULTS
14-3-3sigma is ubiquitously expressed at high levels in normal prostate epithelium. Its expression is significantly decreased in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Ninety percent of samples of prostatic intraepithelial neoplasia had no or low 14-3-3sigma expression. Ninety-seven percent of invasive adenocarcinomas had no or low 14-3-3sigma expression. In most specimens (90%), suppression of 14-3-3sigma expression occurred during the development of prostatic intraepithelial neoplasia from normal epithelium.


CONCLUSIONS
Our data suggest that loss of 14-3-3sigma contributes to the development of prostate adenocarcinoma. 14-3-3sigma expression is significantly decreased during the progression of normal prostatic epithelium to prostatic intraepithelial neoplasia and invasive cancer.
Cheng
Liang
L
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. lcheng@iupui.edu
Pan
Chong-Xian
CX
Zhang
Jian-Ting
JT
Zhang
Shaobo
S
Kinch
Michael S
MS
Li
Lang
L
Baldridge
Lee Ann
LA
Wade
Christopher
C
Hu
Zhiqiang
Z
Koch
Michael O
MO
Ulbright
Thomas M
TM
Eble
John N
JN
D048948:14-3-3 Proteins; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D005092:Exonucleases / Q000096:biosynthesis*; D005095:Exoribonucleases; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human