Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The production of the second messenger molecules diacylglycerol and inositol 1,4,5-trisphosphate is mediated by activated phosphatidylinositol-specific
phospholipase C
(
PLC
) enzymes. We report the enhancement of the phosphoinositide metabolism pathway in KMS-4 and KMS-8 cells, both of which are human colorectal carcinoma cell lines derived from
familial adenomatous polyposis
patients. In these cells, the cellular contents of diacylglycerol and inositol 1,4,5-trisphosphate were constitutively increased and the
PLC
activity in vitro was significantly high, as compared with those in normal colon cells or in other sporadic colorectal carcinoma cells. Northern and Western analyses showed the high expression levels of both
PLC
-gamma 1 and
PLC
-delta 1 in KMS-4 and KMS-8 cells. Moreover, we detected the enhancement of protein-tyrosine kinase activity and tyrosine phosphorylation of
PLC
-gamma 1 in these KMS cells. These results suggest the involvement of activated phosphoinositide signaling pathways in the colorectal tumorigenesis of
familial adenomatous polyposis
.
...
PMID:Enhanced phosphoinositide metabolism in colorectal carcinoma cells derived from familial adenomatous polyposis patients. 752 18
Phosphoinositide-specific
phospholipase C
(
PLC
) isozymes occupy a central role in the signal transduction system by regulating various cellular processes including proliferation and differentiation. In the present study, we examined the contents of PLCs in colorectal adenomas, carcinomas, and normal mucosa obtained from 4
familial adenomatous polyposis
patients to find out whether this enzyme plays any role in the pathogenesis of adenomas and/or carcinomas in
familial adenomatous polyposis
. Radioimmunoassay and immunoblot analysis revealed that in contrast to little difference in
PLC
-beta 1 and
PLC
-delta 1 content, a considerably higher level of
PLC
-gamma 1 was detected in 3 of 4 cases for adenoma and in all cases for carcinoma as compared to normal mucosa. The level of
PLC
-gamma 1 expression increased from normal mucosa to adenoma, and finally to carcinoma progressively. Immunohistochemical findings also confirmed this observation. Likewise, activity of
PLC
-gamma 1 was considerably higher in adenomas and carcinomas than in normal mucosa. These results suggest that
PLC
-gamma 1-mediated signal transduction may play a significant role in the progression of colorectal tumors in patients with
familial adenomatous polyposis
.
...
PMID:Overexpression of phospholipase C-gamma 1 in familial adenomatous polyposis. 817 33
We reported previously the enhanced phosphoinositide metabolism and constitutive activation of phosphoinositide-specific
phospholipase C
(
PLC
) in two colorectal carcinoma cell lines, KMS-4 and KMS-8, derived from
familial adenomatous polyposis
patients. To study the physiological role of enhanced
PLC
activity in these cells, we analyzed the effect of
PLC
inhibitor (PCI) peptides on their growth and cell cycle. N-Myristoylated PCI peptide, myr-PCI(Y), originally developed based on the PCI sequence of
PLC
-gamma 2, inhibited activity of purified
PLC
isoforms in vitro. When myr-PCI(Y) was added to KMS-4 and KMS-8 cultures, it suppressed the production of inositol trisphosphate, DNA synthesis, and cell growth, all of which were induced by serum in both KMS-4 and KMS-8 cells. The number of colonies grown in soft agar was also reduced significantly by treating KMS-8 cells with myr-PCI(Y) peptide. Flow cytometry analysis with propidium iodide labeling revealed marked decreases in the percentage of KMS-8 cells in S phase and increases in G0-G1 by the addition of myr-PCI(Y). On the other hand, myr-PCI(F), in which two of the tyrosine residues in myr-PCI(Y) are replaced by phenylalanine and which does not inhibit phosphatidylinositol 4,5-bisphosphate-hydrolyzing activity in vitro, did not significantly inhibit either inositol trisphosphate production or cell growth. These results indicate that the activation of
PLC
is essential for growth and the transformed properties of these colorectal carcinoma cells.
...
PMID:Growth inhibition by phospholipase C inhibitor peptides of colorectal carcinoma cells derived from familial adenomatous polyposis. 883 58
