title: Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells.
abstract: Astrocytomas are the most common and aggressive primary brain tumors in humans. Invasiveness of these tumors has been attributed in part to deregulation of cell motility-dependent cytoskeletal dynamics that involves actin-binding proteins such as cofilin. Progesterone (P4) has been found to induce migration and invasion of cells derived from breast cancer and endothelium. However, the role of P4 in migration and invasion of astrocytoma cells as well as its effects on astrocytomas cytoskeleton remodeling is not known. In this work we evaluated these aspects in D54 and U251 cells derived from human astrocytomas from the highest degree of malignancy (grade IV, glioblastoma). Our results showed that in scratch-wound assays P4 increased the number of D54 and U251 cells migrating from 3 to 48 h. Both RU486, a P4 receptor (PR) antagonist, and an oligonucleotide antisense against PR significantly blocked P4 effects. Transwell assays showed that P4 significantly increased the number of invasive cells at 24h. As in the case of migration, this effect was blocked by RU486. Finally, by Western blotting, an increase in the cofilin/p-cofilin ratio at 15 and 30 min and a decrease at 30 and 60 min in U251 and D54 cells, respectively, was observed after P4, P4+RU486 and RU486 treatments. These data suggest that P4 increases human astrocytoma cells migration and invasion through its intracellular receptor, and that cofilin activation by P4 is independent of PR action.
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Coyoacán 04510, México, D.F., Mexico.
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Piña-Medina
authors.affiliation: Facultad de Química, Departamento de Biología, UNAM, Ciudad Universitaria, Coyoacán 04510, México, D.F., Mexico.
authors.forename: Valeria
authors.initials: V
authors.lastname: Hansberg-Pastor
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, México, D.F., Mexico.
authors.forename: Aliesha
authors.initials: A
authors.lastname: González-Arenas
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Coyoacán 04510, México, D.F., Mexico.
authors.forename: Marco
authors.initials: M
authors.lastname: Cerbón
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Coyoacán 04510, México, D.F., Mexico. Electronic address: camachoarroyo@gmail.com.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Camacho-Arroyo
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone
keywords: Cofilin; Glioblastoma; Invasion; Migration; Progesterone; RU486