MECHANISMS OF GLUCOCORTICOID INVOLVEMENT IN MOUSE LUNG TUMORIGENESIS
MECHANISMS OF GLUCOCORTICOID INVOLVEMENT IN MOUSE LUNG TUMORIGENESIS
复制标题
DOI：
10.3109/01902149109064424
复制
发表时间：
1991-01-01
影响因子：
1.7
通讯作者：
MALKINSON, AM
中科院分区：
文献类型：
--
作者：
DROMS, KA;MALKINSON, AM
本报告探讨了糖皮质激素（GC）预防小鼠肺肿瘤的可能机制。在使用致癌物脲坦之前，肾上腺切除术（Ax）增加，皮质酮替代减少，肺肿瘤的多样性。Ax增加肺泡上皮细胞的h -3胸腺嘧啶标记指数。在甲基环戊二烯三羰基锰引起的肺损伤引起的代偿性增生期间，给药脲聚糖也能增强肿瘤的多样性。因此，通过刺激靶细胞群的分裂，致癌物质诱导的肿瘤发展被放大。GC对肺泡上皮细胞增殖的调节可能是由Ca++/磷脂依赖性蛋白激酶（PKC）介导的。与肿瘤易感菌株A/J相比，抗瘤菌株C57BL/6J肾上腺皮质酮含量更高，上皮细胞PKC活性更高，肺泡上皮细胞增殖更低。在体外，GC抑制肺上皮源性细胞系的增殖，并增加该细胞系的PKC活性。因此，我们假设GC通过增加肺肿瘤产生的上皮细胞中的PKC含量来防止肺肿瘤的发展；增加的细胞内PKC导致上皮细胞增殖减少，并降低脲聚糖诱导肿瘤发生的可能性。
This report examines a possible mechanism of mouse lung tumor prophylaxis by glucocorticoids (GC). Adrenalectomy (Ax) increased, and corticosterone replacement decreased, lung tumor multiplicity when treatment was begun before administration of the carcinogen, urethan. Ax increased the H-3-thymidine labeling index of alveolar epithelial cells. Tumor multiplicity was also enhanced when urethan was administered during the period of compensatory hyperplasia that occurred in response to lung injury induced by methylcyclopentadienyl manganese tricarbonyl. Thus, carcinogen-induced tumor development was amplified by stimulation of division of the target cell population. GC regulation of alveolar epithelial cell proliferation, and hence tumor susceptibility, may be mediated by the Ca++/phospholipid-dependent protein kinase (PKC). The tumor-resistant strain, C57BL/6J, has greater adrenal corticosterone content, higher epithelial cell PKC activity, and lower alveolar epithelial cell proliferation than the tumor-susceptible strain, A/J. In vitro, GC inhibit proliferation of a lung epithelial-derived cell line and increase PKC activity in that cell line. Thus, we hypothesize that GC protect against lung tumor development by increasing PKC content in the epithelial cells from which lung tumors arise; increased intracellular PKC results in decreased epithelial proliferation, and reduces the probability of induction of tumorigenesis by urethan.