| First Author | Ashtekar A | Year | 2018 |
| Journal | J Clin Endocrinol Metab | Volume | 103 |
| Issue | 11 | Pages | 4135-4145 |
| PubMed ID | 30165401 | Mgi Jnum | J:320950 |
| Mgi Id | MGI:6883451 | Doi | 10.1210/jc.2018-01039 |
| Citation | Ashtekar A, et al. (2018) Alterations in Sod2-Induced Oxidative Stress Affect Endocrine Cancer Progression. J Clin Endocrinol Metab 103(11):4135-4145 |
| abstractText | Context: Although important advances have been made in understanding the genetics of endocrine tumors, cellular physiology is relatively understudied as a determinant of tumor behavior. Oxidative stress and reactive oxygen species are metabolic factors that may affect tumor behavior, and these are, in part, controlled by manganese-dependent superoxide dismutase (MnSod), the mitochondrial superoxide dismutase (encoded by SOD2). Objective: We sought to understand the role of MnSod in the prognosis of aggressive human endocrine cancers and directly assessed the effect of MnSod under- or overexpression on tumor behavior, using established mouse thyroid cancer models. Methods: We performed transcriptome analysis of human and mouse models of endocrine cancer. To address the role of Sod2 in endocrine tumors, we introduced a Sod2 null allele or a transgenic Sod2 overexpression allele into mouse models of benign thyroid follicular neoplasia or aggressive, metastatic follicular thyroid cancer (FTC) and monitored phenotypic changes in tumor initiation and progression. Results: In the thyroid, SOD2/Sod2 was downregulated in FTC but not papillary thyroid cancer. Reduced expression of SOD2 was correlated with poorer survival of patients with aggressive thyroid or adrenal cancers. In mice with benign thyroid tumors, Sod2 overexpression increased tumor burden. In contrast, in mice with aggressive FTC, overexpression of Sod2 reduced tumor proliferation and improved mortality rates, whereas its deficiency enhanced tumor growth. Conclusion: Overall, our results indicate that SOD2 has dichotomous roles in cancer progression and acts in a context-specific manner. |
