Auersperg N
Cancer Res. 1978 Jul;38(7):1872-84.
Normal rat adrenocortical cells grow in vitro in two states of differentiation, depending on culture conditions. Under one set of conditions, they proliferate and are fibroblast shaped, with some myoid cell characteristics and with limited steroidogenic activity. Under alternate conditions they do not replicate and are epithelial-like and similar to adrenocortical secretory cells structurally and steroidogenically. The effects of oncogenic transformation on these cellular responses to culture variables were examined by using the Kirsten murine sarcoma virus-transformed rat adrenocortical line TRA. Transformation eliminated the differential proliferative response of the cells to culture variables and resulted in similar growth rates and high cell densities under all conditions. Horse serum, conducive to epithelial-like growth of nontransformed cells, caused aggregation, whereas fetal calf serum, conducive to fibroblastic growth of untransformed cells, caused dispersed growth in TRA cultures. Variations in dissociation procedures had little effect on growth patterns. Most ultrastructural characteristics of myoid as well as adrenocoritcal differentiation were reduced in TRA cells, although basement membranes and extracellular matrix were produced, but under different conditions than in untransformed cultures. Like normal adrenocortical cells, TRA cells were capable of 20alpha-reduction and delta5-3-beta-dehydrogenation of [4-14C5pregnenolone but, in contrast to untransformed cells, they did not respond to variables in culture conditions by qualitative changes in pregnenolone metabolism, did not produce deoxycorticosterone or corticosterone, and secreted progesterone, a hormone not recovered from untransformed cultures. TRA cells showed no increase in steroidogenic differentiation in response to those culture environment factors that normally cause modulation of the fibroblast-shaped adrenocortical stem cells to more differentiated steroid-secreting cells.
正常大鼠肾上腺皮质细胞在体外根据培养条件以两种分化状态生长。在一组条件下，它们增殖，呈成纤维细胞形状，具有一些肌样细胞特征且类固醇生成活性有限。在交替条件下，它们不复制，呈上皮样，在结构和类固醇生成方面类似于肾上腺皮质分泌细胞。通过使用 Kirsten 小鼠肉瘤病毒转化的大鼠肾上腺皮质系 TRA 研究致癌转化对这些细胞对培养变量反应的影响。转化消除了细胞对培养变量的差异增殖反应，导致在所有条件下生长速率相似且细胞密度高。有利于未转化细胞上皮样生长的马血清会导致细胞聚集，而有利于未转化细胞成纤维细胞样生长的胎牛血清会导致 TRA 培养物中细胞分散生长。解离程序的变化对生长模式影响很小。TRA 细胞中肌样以及肾上腺皮质分化的大多数超微结构特征减少，尽管产生了基底膜和细胞外基质，但与未转化培养物的条件不同。与正常肾上腺皮质细胞一样，TRA 细胞能够对 [4-14C]孕烯醇酮进行 20α-还原和 Δ5-3-β-脱氢，但与未转化细胞相反，它们对培养条件中的变量没有通过孕烯醇酮代谢的定性变化做出反应，不产生脱氧皮质酮或皮质酮，而是分泌孕酮，一种未从未转化培养物中回收的激素。TRA 细胞对那些通常会导致成纤维细胞形状的肾上腺皮质干细胞向更分化的类固醇分泌细胞调节的培养环境因素没有表现出类固醇生成分化的增加。
