Księżakowska-Łakoma Kinga, Żyła Monika, Wilczyński Jacek R
Department of Gynecology, Chair of Obstetrics & Gynecological Surgery, Medical University of Lodz, Lodz, Poland.
Department of Gynecology, Chair of Obstetrics & Gynecological Surgery, Medical University of Lodz, Lodz, Poland ; Department of Gynecology and Oncologic Gynecology, "Polish Mother's Health Center" Research Institute, Lodz, Poland.
Prz Menopauzalny. 2014 May;13(2):136-44. doi: 10.5114/pm.2014.42717. Epub 2014 May 21.
Mitochondria are semi-autonomous organelles of eukaryotic cells. They perform crucial functions such as generating most of the cellular energy through the oxidative phosphorylation (OXPHOS) system and some other metabolic processes. In addition, mitochondria are involved in regulation of cell death and reactive oxygen species (ROS) generation. Also, mitochondria play important roles in carcinogenesis via altering energy metabolism, resistance to apoptosis, increase of production of ROS and mtDNA (mitochondrial genome) changes. Studies have suggested that aerobic glycolysis is high in malignant tumors. Probably, it correlates with high glucose intake of cancerous tissues. This observation is contrary to Warburg's theory that the main way of energy generation in cancer cells is non-oxidative glycolysis. Further studies have suggested that in tumor cells both oxidative phosphorylation and glycolysis were active at various rates. An increase of intracellular oxidative stress induces damage of cellular structure and somatic mutations. Further studies confirmed that permanent activity of oxidative stress and the influence of chronic inflammation damage the healthy neighboring epithelium and may lead to carcinogenesis. For instance, chronic inflammatory bowel disease could be related to high risk of colon adenocarcinoma. The data have shown a role of ROS generation, mtDNA or nDNA alterations and abnormal apoptotic machinery in endometrial cancer progress. Recent studies suggest that mtDNA mutations might play a potential role in endometrial cancer progress and indicate an increase of mitochondrial biogenesis in this cancer. The investigators suggested that MtCOI and MtND6 alteration has an influence on assembly of respiratory complexes in endometrial cancer. In many human cancers, there is a deregulation of the balance between cell growth and death. The tumor cells can avoid apoptosis through a loss of balance between anti- and pro-apoptotic proteins, reduced caspase function and impaired death receptor signaling. Over-expression of the anti-apoptotic BCL-2 gene has also been identified in numerous cancers including colon, thyroid, breast and endometrial cancer. Most studies have found low BCL-2 family gene expression, which could be a sign of blocking apoptosis in breast and endometrial cancer. Moreover, BCL-2 gene expression is correlated with the degree of aggressiveness and differentiation in endometrial cancer. As a result, it could be a valuable predictor of disease progression.
线粒体是真核细胞的半自主细胞器。它们执行关键功能，如通过氧化磷酸化（OXPHOS）系统和其他一些代谢过程产生细胞的大部分能量。此外，线粒体参与细胞死亡调控和活性氧（ROS）生成。而且，线粒体通过改变能量代谢、抗凋亡能力、增加ROS生成以及线粒体DNA（mtDNA，线粒体基因组）变化在致癌过程中发挥重要作用。研究表明恶性肿瘤中糖酵解水平较高。这可能与癌组织对葡萄糖的高摄取有关。这一观察结果与Warburg理论相反，后者认为癌细胞能量产生的主要方式是非氧化糖酵解。进一步研究表明，在肿瘤细胞中，氧化磷酸化和糖酵解都以不同速率活跃进行。细胞内氧化应激增加会导致细胞结构损伤和体细胞突变。进一步研究证实，氧化应激的持续作用以及慢性炎症的影响会损害健康的邻近上皮细胞，并可能导致癌变。例如，慢性炎症性肠病可能与结肠癌的高风险有关。数据显示ROS生成、mtDNA或核DNA（nDNA）改变以及异常凋亡机制在子宫内膜癌进展中发挥作用。近期研究表明，mtDNA突变可能在子宫内膜癌进展中发挥潜在作用，并表明该癌症中线粒体生物发生增加。研究人员认为，MtCOI和MtND6改变会影响子宫内膜癌中呼吸复合体的组装。在许多人类癌症中，细胞生长与死亡之间的平衡失调。肿瘤细胞可通过抗凋亡蛋白和促凋亡蛋白之间失衡、半胱天冬酶功能降低以及死亡受体信号受损来避免凋亡。抗凋亡BCL - 2基因的过表达也在包括结肠癌、甲状腺癌、乳腺癌和子宫内膜癌在内的多种癌症中被发现。大多数研究发现BCL - 2家族基因表达较低，这可能是乳腺癌和子宫内膜癌中凋亡受阻的一个迹象。此外，BCL - 2基因表达与子宫内膜癌的侵袭程度和分化程度相关。因此，它可能是疾病进展的一个有价值的预测指标。
