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. MATERIALS AND 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. CONCLUSION: 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.

Expression of p150 in cervical neoplasia and its potential value in predicting survival.

BACKGROUND: A recently cloned novel p150 protein was found to be overexpressed in human breast carcinoma. To the authors' knowledge, no data on p150 expression in any other human tumors have been published previously. METHODS: To investigate whether the expression of p150 correlated with the clinicopathologic stages of cervical neoplasms or the prognoses of patients with these neoplasms, the authors conducted an immunohistochemical study of archival formalin fixed, paraffin embedded specimens. Seventy-two precancerous lesions (CIN), 75 clinical Stage IB invasive squamous carcinomas, and 20 samples of normal squamous epithelia were included. In addition to p150, the Ki-67 labeling index was assessed as a proliferation parameter. The presence of human papillomavirus was analyzed by in situ DNA hybridization. RESULTS: A significant association of p150 with the grade of atypia in cervical neoplasms was demonstrated. The highest expression of p150 was observed in low grade CIN, with subsequently decreasing expression in high grade CIN and invasive carcinoma. For patients with invasive carcinoma, p150 was significantly correlated with clinical outcome. Patients with high expression of p150 had a better prognosis than those with low p150. Those with regional lymph node metastasis and significant p150 expression had longer relapse free survival than those with insignificant p150 expression. Women whose carcinomas demonstrated vascular space invasion or high microvessel density survived longer when p150 was clearly expressed. p150 behaves as a potential tumor marker during early cervical carcinoma development and is later turned off as cells proceed to more advanced stages of their malignant phenotypes. CONCLUSIONS: p150 is a molecular parameter that might become useful in predicting disease progression and determining the prognoses of patients with invasive cervical carcinoma.

Cloning of a novel protein overexpressed in human mammary carcinoma.

A novel Mr 150,000 protein (p150), which was found to be preferentially expressed in virally and oncogene transformed mouse cells, was partially purified, and the cDNA was cloned. p150 is the largest member of a putative protein family, the molecular function of which is as yet unknown. Its pattern of expression correlates well not only with transformation but also with the dedifferentiated state of several mouse cell lines and cells. Furthermore, human breast carcinoma specimens and normal tissue from the same breast were screened for the presence of the p150 antigen. In all carcinoma samples, Western blotting revealed higher p150 expression levels than that in control tissue from the same patient. Immunohistochemical analyses of the same specimens displayed specific staining of the carcinoma cells.