Increased phospholipase C activity in neoplastic thyroid membrane.
The phospholipase C (PLC)-protein kinase C (PKC) signal transduction pathway appears to be important for cellular growth of many normal and neoplastic tissues. Because alterations in the thyroid-stimulating hormone (TSH) receptor-adenylate cyclase-protein kinase A system in some thyroid tumors do not correlate with tumor size, invasiveness, or metastatic potential, we studied the PLC activity in both normal and neoplastic thyroid tissues from 11 patients. Five of these patients had follicular adenomas and 6 had papillary carcinomas. An 8,000 x g membrane fraction and a 105,000 x g cytosol fraction were prepared from the normal and neoplastic human thyroid tissues. PLC hydrolyzes phosphatidylinositol, 4,5-diphosphate (PIP2) to diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). Phospholipase C activity was determined measuring the hydrolysis of [3H]-PIP2. The activity of PLC in the neoplastic thyroid tissue membrane fraction (20.91 +/- 2.28 nmol PIP2 hydrolyzed/mg protein/120 min) was higher than that in normal thyroid membrane (14.27 +/- 0.82) (p < 0.05). In contrast, PLC activity was similar in the neoplastic (16.12 +/- 0.86 nmol PIP2 hydrolyzed/mg protein/120 min) and normal (16.66 +/- 0.60) cytosol. There was no difference between PLC activity in the membrane fraction from adenomas (21.21 +/- 3.71 nmol PIP2 hydrolyzed/mg protein/120 min) when compared with thyroid carcinomas (20.67 +/- 3.14). Neoplastic thyroid membranes have greater PLC activity than that found in normal thyroid membranes from the same patients. Although PLC activity in benign and malignant thyroid membranes was similar, the increased PLC activity in thyroid neoplasms may be responsible for or contribute to the enhanced growth of some thyroid tumors.
UCSF/Mount Zion Medical Center San Francisco.
K
K
Kobayashi
J K
JK
Shaver
W
W
Liang
A E
AE
Siperstein
Q Y
QY
Duh
O H
OH
Clark
D000236:Adenoma / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D002291:Carcinoma, Papillary / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology*; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000201:enzymology*; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium