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Increased levels of phosphatidylinositol 3‐kinase activity in colorectal tumors
Author(s) -
Phillips Wayne A.,
St. Clair Fiona,
Munday Adam D.,
Thomas Robert J. S.,
Mitchell Christina A.
Publication year - 1998
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19980701)83:1<41::aid-cncr6>3.0.co;2-h
Subject(s) - phosphatidylinositol , kinase , medicine , inositol , pi , phosphorylation , microbiology and biotechnology , biochemistry , biology , receptor
BACKGROUND Phosphatidylinositol 3‐kinase (PI 3‐kinase), an enzyme that phosphorylates inositol phospholipids at the D‐3 position of the inositol ring, has been implicated in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli. In spite of the considerable attention PI 3‐kinase has received with regard to its possible role in the mitogenic pathways in hematopoietic malignancies, there are few reports of investigations into PI 3‐kinase activity in solid tumors. METHODS Colorectal tumor tissue and normal‐appearing colonic mucosa from the same patients were homogenized and solubilized and adjusted to equal protein levels. PI 3‐kinase then was immunoprecipitated from 200 μg of the solubilized tissue using a polyclonal antibody to the p85 subunit of PI 3‐kinase. PI 3‐kinase activity was assessed using phosphatidylinositol as the substrate and the assay product analyzed by thin‐layer chromatography. Phosphorylation of phosphatidylinositol in the D‐3 position was confirmed by high performance liquid chromatography analysis of deacylated and deglycerated products. RESULTS Thirty‐two of the 37 tumors tested (86%) demonstrated increased PI 3‐kinase activity compared with normal‐appearing mucosa from the same patients (overall mean increase ± standard error of the mean = 3.8 ± 0.6‐fold; P < 0.05, Student's t test for paired data). The frequency and extent of increased PI 3‐kinase enzyme activity in tumors did not correlate with clinical parameters or the presence of oncogenic ras mutations. CONCLUSIONS In this study colorectal tumors exhibited enhanced PI 3‐kinase activity compared with normal colonic mucosa, raising the possibility that PI 3‐kinase may be a potential target for new strategies for the treatment of colorectal carcinoma. Cancer 1998;83:41‐47. © 1998 American Cancer Society.