Miele M E, McGary C T, Welch D R
Department of Pathology, Pennsylvania State University College of Medicine, M.S. Hershey Medical Center 17033-0850, USA.
Anticancer Res. 1995 Sep-Oct;15(5B):2065-70.
Manganese superoxide dismutase (MnSOD, encoded by the SOD2 gene mapping to chromosome 6q25) has been implicated as a tumor suppressor and as a metastasis suppressor in some tumor cell lines. We showed that introduction of an intact chromosome 6 into the metastatic melanoma cell line C8161 completely suppressed metastasis but did not affect tumorigenicity (Welch et al., (1994) Oncogene 9:255). The purpose of this study was to test whether SOD2 is the gene responsible for metastasis suppression. MnSOD protein levels of C8161 (measured by Western blot), before and after transfer of chromosome 6, showed no correlation with metastatic potential. To determine whether the lack of correlation was due to mutant, nonfunctional SOD2, a highly metastatic subclone of C8161 (C8161c1.9) was transfected with functional SOD2 or vector control (pSFFV). Metastatic potential and tumorigenicity were unchanged. Southern and Northern blots confirmed the presence of the transfected SOD2; however, total MnSOD protein and antioxidant activity were not significantly altered. These results suggest that levels of MnSOD are highly regulated within C8161 melanoma cells and that SOD2 does not suppress tumor formation nor metastatic potential in all human melanomas.
锰超氧化物歧化酶（MnSOD，由定位于6号染色体6q25的SOD2基因编码）在一些肿瘤细胞系中被认为是一种肿瘤抑制因子和转移抑制因子。我们发现，将完整的6号染色体导入转移性黑色素瘤细胞系C8161可完全抑制转移，但不影响致瘤性（Welch等人，(1994) Oncogene 9:255）。本研究的目的是检验SOD2是否是负责抑制转移的基因。在导入6号染色体前后，C8161的MnSOD蛋白水平（通过蛋白质免疫印迹法测定）与转移潜能均无相关性。为了确定缺乏相关性是否是由于突变的、无功能的SOD2所致，用功能性SOD2或载体对照（pSFFV）转染了C8161的一个高转移性亚克隆（C8161c1.9）。转移潜能和致瘤性均未改变。Southern印迹和Northern印迹证实了转染的SOD2的存在；然而，总MnSOD蛋白和抗氧化活性并未显著改变。这些结果表明，C8161黑色素瘤细胞内的MnSOD水平受到高度调节，并且SOD2在所有人类黑色素瘤中均不抑制肿瘤形成和转移潜能。
