Cardoso Cibele C, Bornstein Stefan R, Hornsby Peter J
Department of Internal Medicine III, University Medical Center, University of Dresden, Germany.
Mol Cell Endocrinol. 2009 Mar 5;300(1-2):175-9. doi: 10.1016/j.mce.2008.10.046. Epub 2008 Nov 13.
Adenomas and nodules of the human adrenal cortex are common, whereas adrenocortical carcinomas are rare. Genes such as IGF2 have been suggested to be important in human adrenocortical tumorigenesis but their role has not been directly investigated. We describe here elements of a system in which hypotheses concerning the molecular basis for the formation of benign and malignant adrenocortical lesions can be experimentally tested. Various viral vectors have been employed in the study of adrenocortical cell biology. Because of the low proliferative rate of primary human adrenocortical (pHAC) cells, a lentiviral system is ideal for transducing these cells with genes that may alter their characteristics or cause them to acquire benign or malignant tumorigenicity. Cultures of pHAC cells were highly infectible with lentiviruses and showed a higher proliferative potential when transduced with a lentivirus encoding IGF2. For tumorigenesis studies of genetically modified adrenocortical cells, we use RAG2(-/-), gammac(-/-) mice. Using this immunodeficient mouse model, we established an orthotopic intra-adrenal cell transplantation technique for adrenocortical cells that should be of value for future studies of the experimental conversion of human adrenocortical cells to a benign or malignant tumorigenic state.
人类肾上腺皮质腺瘤和结节很常见，而肾上腺皮质癌则很罕见。诸如IGF2等基因已被认为在人类肾上腺皮质肿瘤发生过程中很重要，但其作用尚未得到直接研究。我们在此描述了一个系统的要素，在这个系统中，可以通过实验来检验关于良性和恶性肾上腺皮质病变形成的分子基础的假设。各种病毒载体已被用于肾上腺皮质细胞生物学的研究。由于原代人肾上腺皮质（pHAC）细胞的增殖率较低，慢病毒系统非常适合用可能改变其特性或使其获得良性或恶性致瘤性的基因转导这些细胞。pHAC细胞培养物对慢病毒具有高度感染性，并且在用编码IGF2的慢病毒转导时显示出更高的增殖潜力。对于基因改造的肾上腺皮质细胞的肿瘤发生研究，我们使用RAG2（-/-）、γc（-/-）小鼠。利用这种免疫缺陷小鼠模型，我们建立了一种用于肾上腺皮质细胞的原位肾上腺内细胞移植技术，该技术对于未来关于将人肾上腺皮质细胞转化为良性或恶性致瘤状态的实验研究应该具有价值。
