Links between obesity, diabetes and ethnic disparities in breast cancer among Hispanic populations.

Breast cancer is the most prevalent malignancy in women worldwide and is a growing concern due to rising incidence and ongoing ethnic disparities in both incidence and mortality. A number of factors likely contribute to these trends including rising rates of obesity and diabetes across the globe and differences in genetic predisposition. Here, we emphasize Hispanic populations and summarize what is currently known about obesity, diabetes and individual genetic predisposition as they relate to ethnic disparities in breast cancer incidence and mortality. In addition, we discuss potential contributions to breast cancer aetiology from molecular mechanisms associated with obesity and diabetes including dyslipidemia, hyperglycaemia, hyperinsulinaemia, endocrine dysfunction and inflammation. We propose that unique differences in diet and lifestyle coupled with individual genetic predisposition and endocrine/immune dysfunction explain most of the ethnic disparities seen in breast cancer incidence and mortality.

ROCK1 & 2 perform overlapping and unique roles in angiogenesis and angiosarcoma tumor progression.

The serine/threonine protein kinase paralogs ROCK1 & 2 have been implicated as essential modulators of angiogenesis; however their paralog-specific roles in endothelial function are unknown. shRNA knockdown of ROCK1 or 2 in endothelial cells resulted in a significant disruption of in vitro capillary network formation, cell polarization, and cell migration compared to cells harboring non-targeting control shRNA plasmids. Knockdowns led to alterations in cytoskeletal dynamics due to ROCK1 & 2-mediated reductions in actin isoform expression, and ROCK2-specific reduction in myosin phosphatase and cofilin phosphorylation. Knockdowns enhanced cell survival and led to ROCK1 & 2-mediated reduction in caspase 6 and 9 cleavage, and a ROCK2-specific reduction in caspase 3 cleavage. Microarray analysis of ROCK knockdown lines revealed overlapping and unique control of global transcription by the paralogs, and a reduction in the transcriptional regulation of just under 50% of VEGF responsive genes. Finally, paralog knockdown in xenograft angiosarcoma tumors resulted in a significant reduction in tumor formation. Our data reveals that ROCK1 & 2 exhibit overlapping and unique roles in normal and dysfunctional endothelial cells, that alterations in cytoskeletal dynamics are capable of overriding mitogen activated transcription, and that therapeutic targeting of ROCK signaling may have profound impacts for targeting angiogenesis.