Paraoxonase 2 overexpression inhibits tumor development in a mouse model of ovarian cancer

Abstract Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue. Using a mouse xenograft model of OC, we demonstrate that overexpression of PON2 prevents tumor formation. Mechanistically, PON2 decreases OC cell proliferation by inhibiting insulin like growth factor-1 (IGF-1) expression and signaling. Intriguingly, PON2 reduces c-Jun-mediated transcriptional activation of IGF-1 gene by decreasing mitochondrial superoxide generation. In addition, PON2 impairs insulin like growth factor-1 receptor (IGF-1R) signaling in OC cells by altering cholesterol homeostasis, which resulted in reduced caveolin-1/IGF-1R interaction and IGF-1R phosphorylation. Taken together, we report for the first time that PON2 acts as a tumor suppressor in the early stage of OC by reducing IGF-1 production and its signaling, indicating PON2 activation might be a fruitful strategy to inhibit early stage ovarian tumor

Caractérisation des forêts mélangées

International audienceAn appropriate, common interpretation of stand structure characteristics is a key element to better understand forest ecosystem ecology and dynamics. Standards for characterizing the structure, dynamics and productivity of even-aged pure stands are well developed, but such harmonized concepts and methods for mixed forest stands are lacking. Here we compile a comprehensive set of measures, indices and methods at stand level to characterize and evaluate mixed stands. The chapter is organized according to the main components of the structure of forest stands; hence it includes (1) the most relevant concepts and approaches to describe stand density as a key component of stand structure; (2) stand species composition indicators and the most common species diversity indices used in the science of forest growth and yield; (3) how to describe tree distribution patterns, including horizontal spatial pattern, species intermingling and vertical spatial pattern, as well as species-specific height growth and canopy space partitioning; (4) ways to characterize tree-size distribution and growth partitioning among trees of different sizes; and (5) site productivity indices and methods for the comparison of productivity inmixed vs. monospecific stands. Finally we discuss some of the methodological and application challenges related to the reviewed indices and methods which require further attention