A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis

Protein kinase B/Akt has been described as a central mediator of anti-apoptotic signals transduced by the PI3 kinase. Although the role of Akt in the suppression of apoptosis is well elucidated, a potential function of Akt in tumorigenesis and chemoresistance is less intensively documented. In this study, we describe the construction of a novel form of constitutively active Akt1, which relies on the deletion of its pleckstrin homology domain and the insertion of a C-terminal farnesylation sequence. Stable cell lines were generated with MCF10A mammary epithelial cells and A549 human NSCLC cells expressing constitutively active Akt1. Enigneered MCF10A cells were rendered resistant towards apoptosis resulting from loss of cellular substrate attachment (anoikis). We investigated the chemosensitivity of A549 cells expressing farnesylated Akt vs control cells. A profoundly decreased sensitivity towards Mitoxantrone and cisplatin was observed in cells expressing farnesylated Akt. No significant difference in sensitivity however was observed upon treatment with cell cycle specific chemotherapeutic agents like paclitaxel. Our data suggest, that Akt is a central mediator in the suppression of anoikis and modulation of chemotherapy-induced apoptosis. Therefore it represents a promising target for small molecule inhibitors to shift the apoptotic threshold in cancer cells after treatment with standard chemotherapy

Soil fertility in flooded and non-flooded irrigated rice systems

The lowland rice system in Asia makes a major contribution to the global rice supply and is often cited as an example of a sustainable system in which two or three crops of rice are grown in sequence under submerged conditions. However, water shortages are becoming critical in some regions for lowland rice cultivation; and there is high potential in exploring rice cultivation under moisture regimes that save water and also increase productivity. The objective of this article therefore is to analyze the consequences of switching growing of rice from flooded to aerobic conditions on soil fertility and its management. Fertility advantages of submerged rice include amelioration of chemical fertility, preferential accumulation of organic matter and improved availability of major, secondary and selected micronutrients, which contribute to the long-term maintenance of soil fertility and sustainability of the lowland rice system. However, the fertility problems under aerobic rice are better addressed with the crop as a component of a cropping system because continuous growing of aerobic rice in sequence does not seem sustainable due to complex, site-specific chemical and biological constraints