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丙酮酸激酶同工酶与(神经)外胚层肿瘤的去分化

Pyruvate kinase isozymes and dedifferentiation of (neuro-)ectodermal tumors.

作者信息

Oskam R, Van Els C A, Rijksen G, Staal G E

出版信息

Tumour Biol. 1985;6(1):75-87.

PMID:4023564
Abstract

This paper describes the isozyme composition and regulatory properties of pyruvate kinase (PK) from well-differentiated (DMTC) and undifferentiated (AMTC) medullary thyroid carcinomas of the rat. These tumors were chosen as an animal model for human (neuro-)entodermal neoplasms differing in their degree of differentiation. The results were compared with human medullary thyroid carcinomas (MTC) and phaeochromocytomas. AMTC were characterized by increased PK activity, a higher apparent S0.5 for phosphoenolpyruvate, enhanced inhibition by alanine, presence of predominantly M2-type isozyme and loss of M1-type-containing hybrids as compared to DMTC. The alterations in PK isozyme expression and hence kinetic behaviour could not be demonstrated in human MTC or phaeochromocytomas due to the apparently well-differentiated nature of these tumors and the presence of M2-type isozymes. These results are discussed with reference to the nature and significance of PK isozyme shifts found in other tumors. It is suggested that the determination of PK isozyme composition might prove useful in the diagnosis of nueroectodermal neoplasms originating from tissues not primarily expressing M2-type isozyme(s).

摘要

本文描述了来自大鼠高分化(DMTC)和未分化(AMTC)甲状腺髓样癌的丙酮酸激酶(PK)的同工酶组成和调节特性。选择这些肿瘤作为人类(神经)内胚层肿瘤的动物模型,它们在分化程度上有所不同。将结果与人类甲状腺髓样癌(MTC)和嗜铬细胞瘤进行了比较。与DMTC相比,AMTC的特征是PK活性增加、对磷酸烯醇丙酮酸的表观S0.5更高、对丙氨酸的抑制增强、主要存在M2型同工酶以及含M1型的杂种丢失。由于这些肿瘤明显高分化的性质以及M2型同工酶的存在,在人类MTC或嗜铬细胞瘤中无法证明PK同工酶表达的改变以及因此的动力学行为。参照在其他肿瘤中发现的PK同工酶转变的性质和意义对这些结果进行了讨论。有人提出,PK同工酶组成的测定可能对诊断源自非主要表达M2型同工酶的组织的神经外胚层肿瘤有用。

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