Overexpression of p150, a part of the large subunit of the eukaryotic translation initiation factor 3, in colon cancer.
BACKGROUND
P150, a 150 kDa protein, was isolated from virally and oncogene-transformed mouse cell lines, partially purified and cloned. P150 is part of the large subunit of the eukaryotic translation initiation factor 3 with sequence homology to centrosomin A. A significant correlation between p150 expression and malignancy in breast, cervical and esophageal cancer have recently been demonstrated.


METHODS
Here, 110 colorectal carcinomas of different grades and stages, including lymph node and liver metastases were compared to adjacent normal mucosa by immunohistochemistry of P150. Western blot analysis of selected cases confirmed the expression levels determined by immunohistochemistry. Additionally, immuno-electron and laser scanning microscopy (LSM) was performed.


RESULTS
All investigated carcinomas revealed high levels of p150 protein compared to normal adjacent mucosa. The staining intensity was slightly heterogeneous, and positivity was correlated to the tumor grade with statistically significant differences of p150 expression between normal and neoplastic mucosa (p<0.0001, Kruskal-Wallis test). Western blots confirmed higher expression levels of p150 in the tumor. Immunogold labelling and LSM investigation showed high expression levels of p150 on the rough endoplasmic reticulum and polyribosomes, indicating that p150 is translationally active in these tumors.


CONCLUSIONS
Thus, we propose that p150 plays an important role in development and growth of colorectal carcinomas. Furthermore, p150 expression might provide us with reliable information on the biological behaviour of tumors and the clinical course of the disease.
Institute of Neuropathology, Department of Pathology, University Hospital Zurich, Switzerland.
J
J
Haybaeck
T
T
O'Connor
R
R
Spilka
G
G
Spizzo
Ch
Ch
Ensinger
G
G
Mikuz
T
T
Brunhuber
A
A
Vogetseder
I
I
Theurl
W
W
Salvenmoser
H
H
Draxl
R
R
Bänziger
F
F
Bachmann
G
G
Schäfer
M
M
Burger
P
P
Obrist
D002454:Cell Differentiation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D039621:Eukaryotic Initiation Factor-3 / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008875:Middle Aged; D009367:Neoplasm Staging
C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3