MOLECULAR GENETIC EVENTS IN LUNG CANCER

A.我们最近报道了心房利钠因子mRNA表达 小细胞肺肿瘤和肿瘤细胞系的免疫反应性 患有低钠血症的癌症患者不产生精氨酸 加压素高压液相色谱（HPLC）分析 来自低钠血症患者的肿瘤细胞系和肿瘤以及mRNA 心房钠尿因子的表达揭示了细胞内 细胞外肽似乎是心房肌的28个氨基酸形式， 利钠肽，通常在人体血浆中循环的形式。 这些研究是第一个表征异位生产的 心钠素在小细胞肺癌患者中的作用， 已经确定了第三个因子（利钠因子）， 在抗利尿激素分泌不当综合征中假设 （SIADH）。心房利钠因子受体也存在于 小细胞肺癌细胞和细胞对外源性添加的 心房利钠因子与细胞内cGMP的增加， 类似于血管平滑肌细胞上的正常受体。 因此，似乎有功能性ANF受体的表面上， 小细胞肺癌细胞 B。我们回顾了234例肺癌患者的临床过程。在 与123名非小细胞肺癌（NSCLC）患者中没有人相比， 111例小细胞肺癌患者中有18例（16%）发生低钠血症。十 18例有肿瘤细胞系，8例表达ANFmRNA，8例 10个细胞株中有6个同时表达ANF和AVP mRNA。所有10个细胞系均产生ANF mRNA、AVP mRNA或两者兼而有之。 93例小细胞肺癌患者的10种肿瘤细胞系的研究 低钠血症组9例产生ANFmRNA，1例产生AVP mRNA。从 这些研究中，我们观察到，所有研究的肿瘤细胞系， 低钠血症的SCLC患者产生ANF mRNA或AVP mRNA，或两者兼而有之。 心房利钠肽可能是先前假设的第三种 在低钠血症的发病机制中起重要作用 一些患有SIADH的患者。

A. We have recently reported atrial natriuretic factor mRNA expression and immunoreactivity in tumor and tumor cell lines from small cell lung cancer patients with hyponatremia who did not produce arginine vasopressin. High pressure liquid chromoatography (HPLC) analyses of the tumor cell lines and tumors from patients with hyponatremia and mRNA expression of atrial natriuretic factor have revealed that intracellular and extracellular peptide appears to be the 28 amino acid form of atrial natriuretic peptide, the form that normally circulates in human plasma. These studies are the first to characterize the ectopic production of atrial natriuretic peptide in small cell lung cancer patients and may have identified the third factor (natriuretic factor) that has been hypothesized in the syndrome of inappropriate antidiuretic hormone (SIADH). The receptor for atrial natriuretic factor is also present on small cell lung cancer cells and the cells respond to exogenously added atrial natriuretic factor with an increase in intracellular cGMP, similar to the normal receptors on vascular smooth muscle cells. Therefore, there appear to be functional ANF receptors on the surface of small cell lung cancer cells. B. We reviewed the clinical course of 234 lung cancer patients. In contrast to none of the 123 non-small cell lung cancer (NSCLC) patients, 18 of 111 (16%) small cell lung cancer patients had hyponatremia. Ten of these 18 had tumor cell lines available and 8 expressed ANF mRNA, 8 expressed AVP mRNA, and 6 of 10 cell lines produced both ANF and AVP mRNA. All of the 10 cell lines produced ANF mRNA, AVP mRNA, or both. Studies of 10 tumor cell lines from the 93 SCLC patients without hyponatremia showed 9 produced ANF mRNA and one produced AVP mRNA. From these studies we have observed that all tumor cell lines studied from SCLC patients with hyponatremia produce ANF mRNA or AVP mRNA, or both. Atrial natriuretic peptide may be the previously hypothesized third factor and play an important role in the pathogenesis of hyponatremia in some patients with SIADH.