RESUMEN
The human metastasis-associated gene (MTA1), a member of the nucleosome remodeling complex with histone deacetylase activity, is frequently overexpressed in biologically aggressive epithelial neoplasms. Here, we extend this observation to squamous carcinoma cells, which express high levels of MTA1 relative to normal or immortalized keratinocytes. To address functional aspects of MTA1 expression, we established variants of human immortalized keratinocytes (HaCaT cells) by expressing MTA1 cDNA in both the sense and antisense orientations. We demonstrate that (1) forced MTA1 expression enhances migration and invasion of immortalized keratinocytes; (2) MTA1 expression is necessary but not sufficient for cell survival in the anchorage independent state; (3) MTA1 contributes to expression of the anti-apoptotic Bcl-2 family member Bcl-x(L); (4) MTA1 expression in immortalized keratinocytes depends, in part, on activation of the epidermal growth factor receptor (EGFR). These results establish that, in keratinocytes, MTA1 expression contributes to several aspects of the metastatic phenotype including survival in the anchorage independent state, migration, and invasion.
Asunto(s)
Movimiento Celular , Histona Desacetilasas , Queratinocitos/metabolismo , Queratinocitos/patología , Invasividad Neoplásica/patología , Proteínas/metabolismo , Proteínas Represoras , Anoicis , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Adhesión Celular , División Celular , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis de la Neoplasia , Proteínas/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transactivadores , Proteína bcl-XRESUMEN
To ascertain (1) whether male and female adolescent (13-17 years old) psychiatric inpatients endorse comparable reasons for cutting themselves and (2) whether these reasons are correlated with selected psychosocial characteristics of the adolescents, self-reported depression, and hopelessness, the Self-Injury Motivation Scale II (SIMS-II), the Beck Depression Inventory-II, and the Beck Hopelessness Scale were administered to 19 (38%) male and 31 (62%) female adolescents who had cut themselves. Independent t tests found that none of the SIMS-II subscale scores was differentiated by sex, but the Beck Depression Inventory-II total score was significantly correlated with the SIMS-II total, Affect Modulation, Desolation, and Punitive Duality subscale scores. The results are discussed as indicating that male and female adolescent inpatients endorse comparable reasons for cutting themselves and that self-reported depression is positively associated with the number and intensity of different motivations for cutting oneself.