Kobayashi K, Shaver J K, Liang W, Siperstein A E, Duh Q Y, Clark O H
UCSF/Mount Zion Medical Center San Francisco.
Thyroid. 1993 Spring;3(1):25-9. doi: 10.1089/thy.1993.3.25.
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.
磷脂酶C（PLC）-蛋白激酶C（PKC）信号转导途径似乎对许多正常组织和肿瘤组织的细胞生长很重要。由于某些甲状腺肿瘤中促甲状腺激素（TSH）受体-腺苷酸环化酶-蛋白激酶A系统的改变与肿瘤大小、侵袭性或转移潜能无关，我们研究了11例患者正常和肿瘤性甲状腺组织中的PLC活性。其中5例患者患有滤泡性腺瘤，6例患有乳头状癌。从正常和肿瘤性人类甲状腺组织中制备了8000×g的膜部分和105000×g的胞质溶胶部分。PLC将磷脂酰肌醇4,5-二磷酸（PIP2）水解为二酰基甘油（DAG）和肌醇1,4,5-三磷酸（IP3）。通过测量[3H]-PIP2的水解来测定磷脂酶C活性。肿瘤性甲状腺组织膜部分的PLC活性（20.91±2.28 nmol PIP2水解/mg蛋白/120分钟）高于正常甲状腺膜（14.27±0.82）（p<0.05）。相反，肿瘤性（16.12±0.86 nmol PIP2水解/mg蛋白/120分钟）和正常（16.66±0.60）胞质溶胶中的PLC活性相似。腺瘤膜部分的PLC活性（21.21±3.71 nmol PIP2水解/mg蛋白/120分钟）与甲状腺癌（20.67±3.14）相比没有差异。肿瘤性甲状腺膜的PLC活性高于同一患者正常甲状腺膜中的活性。虽然良性和恶性甲状腺膜中的PLC活性相似，但甲状腺肿瘤中PLC活性的增加可能是某些甲状腺肿瘤生长增强的原因或促成因素。
