Mitochondrial DNA content and mass increase in progression from normal to hyperplastic to cancer endometrium

Abstract

BackgroundAn increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1α signalling pathway was previously reported in type I endometrial cancer. The aim of this study has been to evaluate if mtDNA content and the citrate synthase (CS) activity, an enzyme marker of mitochondrial mass, increase in progression from control endometrium to hyperplasia to type I endometrial carcinoma.ResultsGiven that no statistically significant change in mtDNA content and CS activity in endometrium taken from different phases of the menstrual cycle or in menopause was found, these samples were used as control. Our research shows, for the first time, that mtDNA content and citrate synthase activity increase in hyperplastic endometrium compared to control tissues, even if their levels remain lower compared to cancer tissue. In particular, mtDNA content increases seem to precede increases in CS activity. No statistically significant change in mtDNA content and in CS activity was found in relation to different histopathological conditions such as grade, myometrial invasion and stage.ConclusionMtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma.

Growth hormone secretagogues hexarelin and JMV2894 protect skeletal muscle from mitochondrial damages in a rat model of cisplatin-induced cachexia

“…Figure 2C shows a behavior similar to mtDNA: in this case JMV2894 was particularly effective in increasing the level of the protein with respect to hexarelin. We also measured the effect of treatments on mitochondrial mass by evaluating the content of porin and the activity of citrate synthase (CS), an enzyme marker of mitochondrial mass in physiological and pathological conditions 32 . The two markers behaved in a similar way: cisplatin remarkably reduced porin content and CS activity (about 50%) and both GHS effectively antagonized these decreases with JMV2894 displaying a stronger effect (Fig.…”

Mitochondrial changes in endometrial carcinoma: Possible role in tumor diagnosis and prognosis (Review)

“…mtDNA content increase preceded an increase in CS activity. In fact, mtDNA began to increase significantly already in typical hyperplasia while CS activity increased significantly only in atypical hyperplasia (57).…”

The value of MRI in management of endometrial hyperplasia with atypia

“…Endometrial hyperplasia includes non-neoplastic entities (simple and complex hyperplasia without atypia) and precancerous intraepithelial neoplasms (complex endometrial hyperplasia with atypia, CEHA). Strong evidence demonstrates that endometrial hyperplasia is the precursor of endometrial cancer, and if left untreated, it can progress to cancer or may coexist with cancer [2][3][4][5]. Endometrial hyperplasia with atypia is the least common type of hyperplasia but is the type most likely to progress to type 1 endometrial carcinoma (EEC) (30-50%) [6][7][8], whereas simple hyperplasia without atypia is unlikely to progress to malignancy and progestogen therapy is usually recommended [9].…”