Elevated p21-Activated Kinase 2 Activity Results in Anchorage-Independent Growth and Resistance to Anticancer Drug–Induced Cell Death

p21-Activated kinase 2 (PAK-2) seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug–induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug–induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug–induced apoptosis

Prevalence of nasal colonization of methicillin-resistant Staphylococcus aureus in homeless and economically disadvantaged populations in Kansas City

Nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA) plays an important role in the epidemiology and pathogenesis of disease. Situations of close-quarter contact in groups are generally regarded as a risk factor for community acquired MRSA strains due to transmission via fomites and person to person contact. With these criteria for risk, homeless individuals using shelter facilities, including showers and toilets, should be considered high risk for colonization and infection. The aim of this study was to determine the prevalence of nasal colonization of MRSA in a homeless population compared to established rates of colonization within the public and a control group of subjects from a neighboring medical school campus, and to analyze phylogenetic diversity among the MRSA strains. Nasal samples were taken from the study population of 332 adult participants, and analyzed. In addition, participants were surveyed about various lifestyle factors in order to elucidate potential patterns of behavior associated with MRSA colonization. Homeless and control groups both had higher prevalence of MRSA (9.8% and 10.6% respectively) when compared to the general population reported by previous studies (1.8%). However, the control group had a similar MRSA rate compared to healthcare workers (4.6%) while the homeless population had an increased prevalence. Risk factors identified in this study included male gender, age over 50 years and use of antibiotics within the past 3 months. Phylogenetic relationships between 9 of the positive samples from the homeless population were analyzed, showing 8 of the 9 samples had a high degree of relatedness between the spaA genes of the MRSA strains. This indicates that the same MRSA strain might be transmitted from person to person among homeless population. These findings increase our understanding of key differences in MRSA characteristics within homeless populations as well as risks for MRSA associated with being homeless, such as age and gender, which may then be a useful tool in guiding more effective prevention, treatment, and healthcare for homeless individuals