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El papel de la apoptosis en la creación y el mantenimiento del espacio luminal dentro de los acini mamarios normales
Jayanta Debnath1, Kenna R Mills, Nicole L Collins
1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|October 10, 2002
Resumen
La apoptosis elimina selectivamente las células centrales para formar glándulas huecas. Las células cancerosas deben suprimir la apoptosis para llenar el lumen, incluso con una mayor proliferación.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología del desarrollo Biología del desarrollo.
- Biología del cáncer Biología del cáncer.
Sus antecedentes:
- La formación de la arquitectura glandular es crucial para la función del tejido.
- La apoptosis juega un papel clave en la morfogénesis de los tejidos.
- Comprender la formación de la luz es vital para la investigación del cáncer.
Objetivo del estudio:
- Investigar el papel de la apoptosis en la formación y mantenimiento de la luz glandular.
- Para determinar cómo los insultos oncogénicos afectan la arquitectura de la luz.
- Para dilucidar los mecanismos por los cuales las células tumorales superan las restricciones apoptóticas.
Principales métodos:
- Culturas tridimensionales de células epiteliales en vitro.
- Análisis de la apoptosis celular y la proliferación.
- Manipulación de la apoptosis (proteínas de la familia Bcl) y la proliferación (Cyclin D1, HPV E7, ErbB2).
Principales resultados:
- La formación de lumen implica la apoptosis selectiva de las células centrales después de la polarización.
- La inhibición de la apoptosis o la mejora de la proliferación por sí sola no llena el lumen.
- Los insultos oncogénicos combinados (proliferación + anti-apoptosis) o la activación de ErbB2 llenan el lumen.
- La apoptosis contrarresta la proliferación para mantener el espacio luminal.
Conclusiones:
- La apoptosis es esencial para el establecimiento y mantenimiento de estructuras glandulares huecas.
- Las células tumorales requieren la supresión de la apoptosis para proliferar dentro del lumen.
- Dirigir la apoptosis es una estrategia potencial para la terapia del cáncer.
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