Transcriptional regulation of the transforming growth factor-beta2 gene in glioblastoma cells.

The expression of transforming growth factor-beta2 (TGF-beta2) appears to play a strong role in the establishment and progression of glial tumors. In particular, elevated expression of TGF-beta2 appears to be responsible for the impaired cell-mediated immunity often observed in patients with a glioblastoma. This study examined the regulation of the TGF-beta2 at the transcriptional level in the U87MG glioblastoma cell line. We demonstrate that a cAMP response element/activating transcription factor (CRE/ATF) site and an E-box motif located just upstream of the transcription start site are essential for the transcription of the TGF-beta2 gene in U87MG cells. Gel mobility analysis determined that activating transcription factor-1, and possibly cAMP-responsive element binding protein, binds to the CRE/ATF site, and upsteam stimulatory factor (USF) 1 and USF2 bind to the E-box motif. Interestingly, expression of a dominant negative USF protein down-regulates TGF-beta2 activity by 80-95% in glioblastoma cells. We conclude that the binding of transcription factors, in particular the USF proteins, to the TGF-beta2 promoter is essential for its expression and possibly its up-regulation in glioblastomas.

Effects of three Sp1 motifs on the transcription of the FGF-4 gene.

Previous studies have shown that the transcription of the fibroblast growth factor-4 (FGF-4) gene is regulated by a powerful enhancer located approximately three kilobases downstream of the transcription start site. Several conserved cis-regulatory elements in the promoter and the enhancer have been identified, including two Sp1 motifs located in the promoter and one Sp1 motif located in the enhancer. Each of these Sp1 motifs has been shown previously to bind the transcription factors Sp1 and Sp3 in vitro. The main objective of this study was to examine the potential interaction of the FGF-4 promoter and enhancer Sp1 motifs. Using site-directed mutagenesis, we demonstrate that disruption of these sites, individually or in combination, reduce the expression of FGF-4 promoter/reporter gene constructs in embryonal carcinoma cells. Importantly, we demonstrate that disruption of the enhancer Sp1 motif exerts a more pronounced effect on the expression of these constructs than disruption of the promoter Sp1 motifs. We also demonstrate that changing the spacing and the stereo-alignment of the enhancer Sp1 motif, relative to the other cis-regulatory elements of the enhancer, has little effect on the ability of the enhancer to stimulate transcription. Furthermore, embryonic stem cells that contain two disrupted Sp1 alleles were used to demonstrate that the transcription factor Sp1 is not necessary for expression of the endogenous FGF-4 gene. Finally, the significance of these findings relative to a looping model for the transcriptional activation of the FGF-4 gene is discussed.

The relationship between sexual abuse and purging: findings from community-wide surveys of female adolescents.

OBJECTIVE: The first objective of this study was to examine the relationship between sexual abuse and a bulimic behavior, namely purging, with a large sample of female adolescents. If sexual abuse was found to be significantly related to bulimia, then the second objective was to determine if the relationship between abuse and purging remained significant when other factors were controlled. METHOD: Two different analyses were conducted to address the questions outlined above--a contingency table chi-square test and a logistic regression analysis. A sample of 7,903 female adolescents was drawn from a large Midwestern state. RESULTS: The results of the bivariate analysis provide evidence that a relationship exists between sexual abuse and purging. However, the relationships between sexual abuse and purging did not remain significant when several other factors, including physical abuse, were included in the analysis. Several individual (a history of physical abuse and religiosity), familial (i.e., family support and parent-adolescent communication), and extra-familial (i.e., other adult support) factors were significantly related to purging. CONCLUSIONS: The data did not find a significant relationship between sexual abuse and purging when individual, familial, and extra-familial variables were included in the logistic regression. Unlike most earlier studies that focused on clinical samples, this study drew from a larger, more representative sample of female adolescents. The identification of significant predictors of purging at the individual, familial, and extra-familial levels suggests the importance of examining multiple levels of the teen's ecology for factors that may influence this behavior.

Sexual abuse history and number of sex partners among female adolescents.

A survey completed 1996 of 10,868 adolescent females from one Midwestern state indicates that 10% had experienced sexual abuse by an adult or by someone older than themselves-9% in the past and 1% in an ongoing situation. Past and current victims of sexual abuse had had more sexual partners during the past year (2.3 and 1.2, respectively) than their peers who had never been sexually abused (0.5). Regardless of sexual abuse history, teenagers whose activities were closely monitored by their parents, who received high levels of parental support and whose parents disapproved of teenagers having sex had fewer sexual partners than other adolescents. Respondents who had experienced physical abuse in addition to sexual abuse were at further increased risk of having had multiple sexual partners. Overall, sexually abused adolescents with a supportive family had fewer recent partners than those from a less supportive family environment; family context had less influence on number of partners among respondents with no history of sexual abuse.

Factors related to the achievement and adjustment of young African American children.

Data from the National Longitudinal Survey of Yough (NLSY) were used to examine factors related to the achievement and adjustment of African American children in the early elementary grades. All African American children between the ages of 6 and 9 years for whom data were available in the NLSY were included in this study (N = 378). Consistent with past research, there was a positive relation between the number of risk factors children were exposed to and the probability that they were experiencing academic or behavioral problems. Favorable outcomes in the cognitive and social-emotional domains (i.e., scoring in the top quartile for this sample) were associated with high scores on an "advantage index." The need for more research on successful African American children is discussed.

Predictors of the quality of the home environment that adolescent mothers provide for their school-aged children.

The primary question addressed in this study is, What factors distinguish between adolescent mothers with school-aged children who are providing relatively supportive home environments for their children, and their peers who are providing less supportive care? Data from the National Longitudinal Survey of Youth merged mother- child data set were used to address this question. Variables from four major categories were useful in identifying mothers who were at greatest risk for providing less supportive environments: (1) characteristics of the mother, (2) characteristics of the family of origin, (3) current SES level, and (4) the composition of the mother's household.