RESUMO
Advanced prostate cancer preferential metastasis to bone is associated with osteomimicry. MINDIN is a secreted matrix protein upregulated in prostate tumors that overexpresses bone-related genes during prostate cancer progression. Na+/H+ exchanger regulatory factor (NHERF-1) is a scaffold protein that has been involved both in tumor regulation and osteogenesis. We hypothesize that NHERF-1 modulation is a mechanism used by MINDIN to promote prostate cancer progression. We analyzed the expression of NHERF-1 and MINDIN in human prostate samples and in a premetastatic prostate cancer mouse model, based on the implantation of prostate adenocarcinoma TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) cells in immunocompetent C57BL/6 mice. The relationship between NHERF-1 and MINDIN and their effects on cell proliferation, migration, survival and osteomimicry were evaluated. Upregulation of MINDIN and downregulation of NHERF-1 expression were observed both in human prostate cancer samples and in the TRAMP-C1 model. MINDIN silencing restored NHERF-1 expression to control levels in the mouse model. Stimulation with MINDIN reduced NHERF-1 expression and triggered its mobilization from the plasma membrane to the cytoplasm in TRAMP-C1 cells. MINDIN-dependent downregulation of NHERF-1 promoted tumor cell migration and proliferation without affecting osteomimicry and adhesion. We propose that MINDIN downregulates NHERF-1 expression leading to promotion of processes involved in prostate cancer progression.
RESUMO
Lifelong learning (LLL) is an essential feature for the doctor to keep clinically updated and has been described as an indicator of competence and professionalism. The aim of this study was to evaluate the association between career satisfaction in psychiatry, lifelong learning, and commitment in scientific activities, taking into account other personal and professional effects. The survey was sent to 453 national psychiatrists and 190 surveys (41.9%) were completed online and validated. The Jefferson Scale of Physician Lifelong Learning (JSPLL) was used to assess the level of LLL for each doctor. The results of the analysis of JSPLL showed that participants more satisfied with their career have greater motivation and invest more in the LLL. Furthermore, participants who were more satisfied with their career had a higher percentage of scientific activity in the last year. Multiple linear regression with these two effects in the model revealed a positive association between career satisfaction in psychiatry, LLL and the publication of scientific papers, leading to the main conclusion that satisfaction with a career in psychiatry has a significant correlation with LLL and with involvement in scientific activities.