Amstad P A, Liu H, Ichimiya M, Berezesky I K, Trump B F
Department of Pathology, University of Maryland, Baltimore 21201, USA.
Carcinogenesis. 1997 Mar;18(3):479-84. doi: 10.1093/carcin/18.3.479.
Manganese superoxide dismutase (MnSOD) has been found to be depleted in a variety of tumor cells as well as in in vitro transformed cell lines, suggesting that MnSOD may function as an anticarcinogen by protecting the cell from oxidant-induced carcinogenesis. The relationship between MnSOD expression and tumor promotion was studied by transfection of a human MnSOD cDNA into the promotable mouse epidermal cell line JB6 clone41. The effect of MnSOD overexpression on the promotion-sensitive phenotype of JB6 cells was assessed by measuring growth characteristics such as growth rate and the ability to form colonies in soft agar. Compared with the parental and vector-transfected (gpt) control cells, MnSOD-overexpressing cells had a slower growth rate and their ability to form colonies in soft agar was significantly decreased in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. Since the transformation-sensitive phenotype of JB6 clone41 cells is associated with increased expression of the transcription factor AP-1, we compared c-jun and c-fos mRNA expression in MnSOD-transfected and control JB6 cells. Overexpression of MnSOD led to a significant decrease in c-jun and c-fos expression in response to treatment with TPA or the oxidant promoter superoxide. These findings indicate that the promotion-sensitive phenotype of JB6 clone41 cells can be reverted by increasing MnSOD intracellularly. A possible mechanism is that elevated MnSOD expression might change the intracellular redox state by altering the balance of reactive oxygen species. This could lead to a modulation of TPA and oxidant-induced signal transduction pathways controlling cell growth and differentiation.
锰超氧化物歧化酶（MnSOD）已被发现在多种肿瘤细胞以及体外转化细胞系中含量降低，这表明MnSOD可能通过保护细胞免受氧化剂诱导的致癌作用而发挥抗癌剂的功能。通过将人MnSOD cDNA转染到可促进的小鼠表皮细胞系JB6 clone41中，研究了MnSOD表达与肿瘤促进之间的关系。通过测量生长特性，如生长速率和在软琼脂中形成集落的能力，评估了MnSOD过表达对JB6细胞促进敏感表型的影响。与亲本细胞和载体转染（gpt）对照细胞相比，过表达MnSOD的细胞生长速率较慢，并且在12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）处理后，它们在软琼脂中形成集落的能力显著降低。由于JB6 clone41细胞的转化敏感表型与转录因子AP - 1的表达增加有关，我们比较了MnSOD转染的JB6细胞和对照JB6细胞中c - jun和c - fos mRNA的表达。MnSOD的过表达导致在TPA或氧化剂启动子超氧化物处理后c - jun和c - fos的表达显著降低。这些发现表明，通过在细胞内增加MnSOD，可以逆转JB6 clone41细胞的促进敏感表型。一种可能的机制是，升高的MnSOD表达可能通过改变活性氧物种的平衡来改变细胞内氧化还原状态。这可能导致对控制细胞生长和分化的TPA和氧化剂诱导的信号转导途径的调节。
