Dept. Radiation Oncology, 2nd Hospital affiliated to Jilin University, Changchun, China.
Neoplasma. 2012;59(3):269-81. doi: 10.4149/neo_2012_035.
Homeostasis is maintained by the interplay of multiple factors that directly or indirectly regulate cell proliferation and cell death. Complex multiple interactions between cells and the extracellular matrix occur during acinar morphogenesis and changes in these might indicate carcinogenesis of cells from a normal to a malignant, invasive phenotype. In this study, the human prostatic epithelial cell line RWPE-1 was cultured under three-dimensional (3-D) culture conditions, and the effect of ionizing radiation on acinar morphogenesis and its association with autophagy were discussed. The results illustrated that formation of specific spheroid (acinar) structures was detectable under 3-D culture conditions. Radiation induced the disruption of acini in different cell models using either gene overexpression (Akt) or gene knock-down (Beclin 1 and ATG7). Introduction of Akt not only accelerated the growth of cells (i.e., caused the cells to manifest elongating and microspike-like structures that are obviously different from structures seen in wild-type RWPE-1 cells under two-dimensional conditions), but also changed their morphological characteristics under 3-D culture conditions. Knock-down of autophagy-related genes (Beclin 1 and ATG7) increased the radiosensitivity of cells under 3-D culture conditions, and cells died of non-apoptotic death after radiation. The results suggested that ionizing radiation may change the cell phenotype and the formation of acini. Additionally even the autophagy mechanism may play a role in these processes.
内稳态是通过多种因素的相互作用来维持的，这些因素直接或间接地调节细胞增殖和细胞死亡。在腺泡形态发生过程中，细胞与细胞外基质之间会发生复杂的相互作用，这些变化可能表明细胞从正常向恶性、侵袭性表型的癌变。在这项研究中，培养人前列腺上皮细胞系 RWPE-1 处于三维（3-D）培养条件下，并讨论了电离辐射对腺泡形态发生的影响及其与自噬的关系。结果表明，在 3-D 培养条件下可检测到特定的球体（腺泡）结构的形成。辐射诱导不同细胞模型中的腺泡破坏，使用基因过表达（Akt）或基因敲低（Beclin 1 和 ATG7）。Akt 的引入不仅加速了细胞的生长（即导致细胞表现出伸长和微刺状结构，这与二维条件下野生型 RWPE-1 细胞的结构明显不同），而且改变了它们在 3-D 培养条件下的形态特征。自噬相关基因（Beclin 1 和 ATG7）的敲低增加了细胞在 3-D 培养条件下的辐射敏感性，并且细胞在辐射后死于非凋亡性死亡。结果表明，电离辐射可能改变细胞表型和腺泡的形成。此外，即使自噬机制也可能在这些过程中发挥作用。
