Expression of mTOR signaling pathway markers in prostate cancer progression.
BACKGROUND
The PI3K/AKT/mTOR pathway is central to prostate cancer progression. A preliminary investigation of immuno-histochemical expression of mammalian target of rapamycin (mTOR) pathway markers was undertaken to identify patterns of expression in prostate tissue.


METHODS
Immunohistochemistry was performed on a custom-made prostate tissue array. Mean long scores and variability of long scores for each marker were recorded for normal lumenal cells, prostate intraepithelial neoplasia (PIN), and cancer.


RESULTS
Expression of PTEN decreased and mTOR signaling pathway markers increased in PIN and in cancer as compared to normal cells in the majority of samples. Overexpression of 4E-BP1 and p-4E-BP1 was observed in PIN and cancer. However, in cancer, the overexpression of 4E-BP1 was significantly higher than with any other marker.


CONCLUSIONS
Results suggest that 4E-BP1 overexpression is strongly associated with prostate cancer, especially when combined with PTEN and mTOR expression data. Hierarchical clustering analysis utilizing PTEN, mTOR, and 4E-BP1 separated normal from cancer cell populations in most cases.
Kremer
Celeste L
CL
Arizona Cancer Center, University of Arizona, 1525 N. Campbell Avenue, Tucson, AZ 85724, USA.
Klein
Rob R
RR
Mendelson
Jenny
J
Browne
Walden
W
Samadzedeh
Linda K
LK
Vanpatten
Kristie
K
Highstrom
Lindsey
L
Pestano
Gary A
GA
Nagle
Raymond B
RB
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D010750:Phosphoproteins / Q000032:analysis*; D011467:Prostate / Q000737:chemistry / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase