Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis.

PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is mutated in a variety of human cancers. We screened the colon cancer cell lines previously established in our laboratory for PIK3CA mutations and found that four of them harbored gain of function mutations. We have now compared a panel of mutant and wild-type cell lines for cell proliferation and survival in response to stress. There was little difference in PI3K activity between mutant PIK3CA-bearing cells (mutant cells) and wild-type PIK3CA-bearing cells (wild-type cells) under optimal growth conditions. However, the mutant cells showed constitutive PI3K activity during growth factor deprivation stress (GFDS), whereas PI3K activity decayed rapidly in the wild-type cells. Importantly, constitutively active PI3K rendered the mutant cells resistant to GFDS-induced apoptosis relative to the wild-type cells, indicating a biological advantage under stress conditions that is imparted by the mutant enzymes. Compared with the wild-type cells, the mutant cells were hypersensitive to the apoptosis induced by the PI3K inhibitor LY294002. In addition, PIK3CA small interfering RNA significantly decreased DNA synthesis and/or induced apoptosis in the mutant cells but not in the wild-type cells. Furthermore, ecotopic expression of a mutant PIK3CA in a nontumorigenic PIK3CA wild-type cell line resulted in resistance to GFDS-induced apoptosis, whereas transfection of wild-type PIK3CA or empty vector had little effect. Taken together, our studies show that mutant PIK3CA increases the capacity for proliferation and survival under environmental stresses, such as GFDS while also imparting greater dependency on the PI3K pathway for proliferation and survival

RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design

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Perceptions of psychosocial support groups by parents who have a child with diabetes: A needs analysis

Psychosocial support groups play an important role in assisting parents to understand and manage the demands of having a child with diabetes. Actual participation in such groups is marred by problems of poor uptake, irregular attendance and attrition. A survey was conducted with a convenience sample of parents to determine their knowledge needs about preferred program characteristics, the management of diabetes, perceived barriers to program participation, and factors facilitating group attendance. A response rate of 66% (n=40) was achieved. Parents favoured a program that was only conducted monthly or three to six times a year, held during the evening or weekend and of two or three hours duration. Parents were keen to know more about new developments in the treatment of diabetes, and strategies to assist their child when they refuse medication or treatment. The most commonly reported barriers to group attendance were distance, timing of groups, and employment demands. Participants were more likely to attend a support group in order to learn new information or skills, keep up to date, as well as meet parents in the same situation. Support groups need to address both content and practical issues for enhanced support and empowerment of families