These results suggest that ML SA1 miR-17-92 is necessary for Ets1�CEts2/Mycdependent transformation, but does not exclude the requirement for additional target genes that could be required for malignant transformation. In summary, we have shown that Ets1 and Ets2 act in redundant fashion to elicit HrasG12V-mediated transformation of MEFs through the activation of c-Myc and miR-17-92. Previous work has implicated Ets1/Ets2 and c-Myc collaboration in invasive breast cancer and in thyroid cancer in humans. Perhaps more relevant to the MEF model used here, amplification and overexpression of c-Myc or N-myc genes and miR-17-92 have been reported in osteosarcoma and rhabmyosarcoma. Whether our findings are relevant to these human cancers remains to be determined. 31-phosphorus magnetic resonance spectroscopy is a unique tool to investigate human myocardial high-energy phosphate Tetrodotoxin citrate metabolism in vivo. The ratios between phosphocreatine and adenosine-triphosphate obtained by 31P MRS are mainly used as an important physiological index for cardiac energy metabolism. The myocardial HEP metabolism is characterized by a remarkable metabolic stability maintaining almost constant levels of PCr and ATP during increases of workload. This metabolic homeostasis, also known as ����stability paradox����, is enabled by a complex cellular regulation of mitochondrial respiration, which has extensively reviewed by Saks et al.. Consequently, the PCr/ATP ratio reflects the creatine rephosphorylation rate and, therefore, the mitochondrial function in the myocardium. Mitochondrial insufficiency can be caused by defects in key mitochondrial enzymes, increased mitochondrial proton leak, impaired supply of reducing equivalents or insufficient mitochondrial PO2. Previous 31P MRS studies have shown that cardiac PCr/ATP ratios are significantly but unspecifically reduced in ischemic and structural heart diseases as well as in diabetes and other metabolic disorders. Furthermore, several previous studies have shown that the cardiac PCr/ATP ratios are clearly reduced in patients suffering from hereditary disorders with mitochondrial involvement. Our study group has shown that cardiac high-energy metabolism correlates positively with exercise capacity and negatively with cardiovascular risk factors. We also detected a significant effect of age on cardiac high-energy metabolism, showing a decrease in left ventricular PCr/ATP ratio with age.