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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Extracellular protein kinase A as a cancer biomarker: Its expression by tumor cells and reversal by a myristate-lacking Cα and RlIβ subunit overexpression
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Extracellular protein kinase A as a cancer biomarker: Its expression by tumor cells and reversal by a myristate-lacking Cα and RlIβ subunit overexpression

机译：细胞外蛋白激酶A作为癌症的生物标志物：其在肿瘤细胞中的表达以及肉豆蔻缺乏的Cα和RlIβ亚基过度表达的逆转

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Overexpression of cAMP-dependent protein kinase (PKA) type I isozyme is associated with cell proliferation and neoplastic trans- formation. The presence of PKA on the external surface of LS-174T human colon carcinoma cells has been shown. Here. we show that cancer cells of various cell types excrete PKA into the conditioned medium. This extracellular PKA (ECPKA) is present in active, free catalytic subunit (C Subunit) form. and its activity is specifically inhibited by PKA inhibitory protein, PKl. Overexpression of the Cα or Rlα Subunit gene of PKA in an expression vector. which up- regulates intracellular PKA type l, markedly up-regulates ECPKA expression. In contrast, overexpression of the Rllβ subunit. which eliminates PKA type l, up-regulates PKA type II, and reverts the transformed phenotype, down-regulates ECPKA. A mutation in the Cα gene that prevents myristylation allows the intracellular PKA up-regulation but blocks the ECPKA increase, suggesting that the NHz-terminal myristyl group of Cα is required for the ECPKA expression. In serum of cancer patients, the ECPKA expression is up-regulated 10-fold as compared with normal serum. These re- sults indicate that the ECPKA expression is an ordered cellular response of a living cell to actively exclude excess intracellular PKA molecules from the cell. This phenomenon is up-regulated in tumor cells and has an inverse relationship with the hormone dependency of breast cancer. Thus. the extracellular PKA may serve as a potential diagnostic and prognostic marker for cancer.
机译：cAMP依赖性蛋白激酶（PKA）I型同工酶的过表达与细胞增殖和肿瘤转化有关。已经证明在LS-174T人结肠癌细胞的外表面上存在PKA。这里。我们显示了各种细胞类型的癌细胞将PKA排泄到条件培养基中。这种细胞外PKA（ECPKA）以活性，游离催化亚基（C亚基）形式存在。并且其活性被PKA抑制蛋白PK1特异性抑制。 PKA的Cα或Rlα亚基基因在表达载体中的过表达。上调l型细胞内PKA的蛋白，显着上调ECPKA的表达。相反，Rllβ亚基的过表达。它消除了I型PKA，上调了PKA II型，还原了转化的表型，下调了ECPKA。阻止肉豆蔻酰化的Cα基因突变允许细胞内PKA上调，但阻止了ECPKA的增加，表明ECPK​​A表达需要Cα的NHz末端肉豆蔻基。在癌症患者的血清中，与正常血清相比，ECPKA表达上调了10倍。这些结果表明，ECPKA表达是活细胞有序的细胞反应，可以主动从细胞中排除过量的细胞内PKA分子。这种现象在肿瘤细胞中被上调，并且与乳腺癌的激素依赖性成反比。从而。细胞外PKA可以作为潜在的癌症诊断和预后标志物。

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