The emerging role of GATA transcription factors in development and disease

The GATA family of transcription factors consists of six proteins (GATA1-6) which are involved in a variety of physiological and pathological processes. GATA1/2/3 are required for differentiation of mesoderm and ectoderm-derived tissues, including the haematopoietic and central nervous system. GATA4/5/6 are implicated in development and differentiation of endoderm- and mesoderm-derived tissues such as induction of differentiation of embryonic stem cells, cardiovascular embryogenesis and guidance of epithelial cell differentiation in the adult

The N-myc downstream regulated gene (NDRG) family: diverse functions, multiple applications

The N-myc downstream regulated gene (NDRG) family of proteins consists of 4 members, NDRG1-4, which are well conserved through evolution. The first member to be discovered and responsible for the family name was NDRG1, because its expression is repressed by the proto-oncogenes MYCN and MYC. All family members are characterized by an alpha/beta hydrolase-fold motif; however, the precise molecular and cellular function of these family members has not been fully elucidated. Although the exact function of NDRG family members has not been clearly elucidated, emerging evidence suggests that mutations in these genes are associated with diverse neurological and electrophysiological syndromes. In addition, aberrant expression as well as tumor suppressor and oncogenic functions affecting key hallmarks of carcinogenesis such as cell proliferation, differentiation, migration, invasion, and stress response have been reported for several of the NDRG proteins. In this review, we summarize the current literature on the NDRG family members concerning their structure, origin, and tissue distribution. In addition, we review the current knowledge regarding the regulation and signaling of the NDRG family members in development and normal physiology. Finally, their role in disease and potential clinical applications (their role as detection or prognostic markers) are discusse

Childhood and adolescent energy restriction and subsequent colorectal cancer risk: results from the Netherlands Cohort Study

International audienceBackground: Energy restriction during childhood and adolescence is suggested to lower colorectal cancer (CRC) risk. We investigated this in the Netherlands Cohort Study. Methods: Information on diet and other risk factors was collected by a baseline questionnaire in 1986 when cohort members were 55-69 years of age (n=120,852). Three indicators of early life exposure to energy restriction were assessed: father's employment status during the Economic Depression (1932-40), and place of residence during World War 2 years (1940-44) and the 'Hunger Winter' (1944-45); a severe famine. Using the case-cohort approach, incidence rate ratios (RR) and 95% confidence intervals (CI) were calculated for total colorectal, proximal colon, distal colon, rectosigmoid, and rectal cancers, according to the three time periods of energy restriction. After 16.3 years of follow-up, 2573 cases were available for multivariate analyses. Results: Men who lived in a western city during the Hunger Winter and therefore exposed to the highest degree of energy restriction, had a statistically significant lower risk of developing CRC (RR: 0.77, 95% CI: 0.63-0.94), and tumors of the proximal colon (RR: 0.68, 95% CI: 0.49-0.94) and rectum (RR: 0.66, 95% CI: 0.47-0.92). In women, non-statistically significant inverse associations were observed for tumors of the distal colon, rectosigmoid, and rectum. Inverse associations were also observed between the other two exposure times and studied endpoints, though not statistically significant. Conclusions: This unique observational evidence suggests that severe energy restriction during childhood and adolescence may lower CRC risk, especially in men, thus providing insight regarding the role of energy intake during early life in CRC development