Cooperativity between oncogenic mutations is recognized as a fundamental feature of malignant transformation, and it may be mediated by synergistic regulation of the expression of pro-and antitumorigenic target genes. However, the mechanisms by which oncogenes and tumor suppressors coregulate downstream targets and pathways remain largely unknown. Here, we used ChIP coupled to massively parallel sequencing (ChIP-seq) and gene expression profiling in mouse prostates to identify direct targets of the tumor suppressor Nkx3.1. Further analysis indicated that a substantial fraction of Nkx3.1 target genes are also direct targets of the oncoprotein Myc. We also showed that Nkx3.1 and Myc bound to and crossregulated shared target genes in mouse and human prostate epithelial cells and that Nkx3.1 could oppose the transcriptional activity of Myc. Furthermore, loss of Nkx3.1 cooperated with concurrent overexpression of Myc to promote prostate cancer in transgenic mice. In human prostate cancer patients, dysregulation of shared NKX3.1/MYC target genes was associated with disease relapse. Our results indicate that NKX3.1 and MYC coregulate prostate tumorigenesis by converging on, and crossregulating, a common set of target genes. We propose that coregulation of target gene expression by oncogenic/tumor suppressor transcription factors may represent a general mechanism underlying the cooperativity of oncogenic mutations during tumorigenesis.
Men on the Move-Nashville was a quasi-experimental, 10-week pilot physical activity intervention. A total of 40 overweight or obese African American men ages 30 to 70 (mean age = 47) enrolled in the intervention. Participants attended 8 weekly, 90-minute small group sessions with a certified personal trainer. Each session consisted of discussions aimed to educate and motivate men to be more physically active, and an exercise component aimed to increase endurance, strength, and flexibility. Throughout each week, men used wearable activity trackers to promote self-monitoring and received informational and motivational SMS text messages. Of the 40 enrolled men, 85% completed the intervention, and 80% attended four or more small group sessions. Additionally, 70% of participants successfully used the activity tracker, but only 30% of men utilized their gym memberships. Participants benefited from both the small group discussions and activities through increasing social connection and guidance from their trainer and group members. These African American men reported being motivated to engage in physical activity through each of these technologies. Men reported that the activity trackers provided an important extension to their social network of physically active people. The intervention resulted in significant increases in men's self-reported levels of light, moderate, vigorous, and sports-related physical activities, and high-density lipoprotein cholesterol levels, and significant decreases in weight and body fat percentage with small, moderate and large effects shown. Including technology and didactic components in small group-based interventions holds promise in motivating African American men to increase their physical activity.
African American men are less likely than white men to meet physical activity recommendations, and few physical activity interventions have focused on the unique needs of African American men. Because health is not more important to men than fulfilling the roles of a provider or other socially important roles, one of the biggest challenges in creating interventions for African American men is helping them identify reasons that they should prioritize both health and life goals. In a recent pilot physical activity intervention for 30-70 year old African American men, we used Self-determination Theory and Motivational Interviewing principles to create worksheets that helped men identify their core values and life goals and asked them to describe how their values and goals were related to health and physical activity. We used basic statistics and thematic analysis to identify and examine key sources of motivation for men to be healthier and more physically active. We found that being healthy, a good Christian, a good spouse/partner, disciplined, and successful were among men's most important life goals. This article highlights a strategy for identifying key sources of motivation in African American men's lives and key themes that can be used in to enhance future interventions.
African American men have high rates of chronic disease morbidity and mortality associated with their low rates of fruit and vegetable consumption. In an effort to inform tailored behavioral interventions for this demographic, we sought to assess if men with healthier eating practices viewed their environment differently than those who ate less healthy. We segmented participants into high/low healthy eating categories based on the daily fruit and vegetable serving recommendations from the U.S. Department of Agriculture to determine if differences among environmental and social barriers were associated with different healthy eating patterns. We found key differences between men who consumed the recommended amount of fruits and vegetables (five or more servings/day, high healthy eating) and men who did not (low healthy eating). Men who consumed recommended levels of fruits and vegetables found eating healthy to be easy, and they described how they were able to overcome barriers such as the cost of healthy food, their limited knowledge of nutrition guidelines, and their lack of willpower to make healthier food choices. Men with healthier eating practices also identified individuals, plans, and resources they used or could use to help them have healthier eating practices. Conversely, men who were not eating recommended levels of fruits and vegetables also found eating healthy to be easy; however, they identified barriers limiting their access and did not articulate strategies to overcome these perceived barriers. Many of these men also indicated that they did not have social support to help them engage in healthier eating practices. These findings highlight the need to understand how African American men's conceptualization of environmental resources and social supports relate to their eating practices.
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