Giraldi, Tiziana
(2010)
Androgen-induced migration in NIH3T3 mouse fibroblasts: role of AR association with Filamin A.
[Tesi di dottorato]
(Inedito)
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
Italiano |
| Titolo: |
Androgen-induced migration in NIH3T3 mouse fibroblasts: role of AR association with Filamin A. |
| Autori: |
| Autore | Email |
|---|
| Giraldi, Tiziana | tiziana.giraldi@unina.it |
|
| Data: |
23 Novembre 2010 |
| Numero di pagine: |
98 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Biologia e patologia cellullare e molecolare "L. Califano" |
| Scuola di dottorato: |
Medicina molecolare |
| Dottorato: |
Patologia e fisiopatologia molecolare |
| Ciclo di dottorato: |
23 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Avvedimento, Vittorio Enrico | avvedim@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Migliaccio, Antimo | antimo.migliaccio@unina2.it |
|
| Data: |
23 Novembre 2010 |
| Numero di pagine: |
98 |
| Parole chiave: |
androgens, migration, AR/ filamin A complex |
| Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/04 - Patologia generale |
[error in script]
[error in script]
| Depositato il: |
10 Dic 2010 10:28 |
| Ultima modifica: |
30 Apr 2014 19:43 |
| URI: |
http://www.fedoa.unina.it/id/eprint/7943 |
| DOI: |
10.6092/UNINA/FEDOA/7943 |
Abstract
Androgen stimulation triggers rapid activation of various signaling effectors in target cells (Migliaccio et al. 2000; Castoria et al. 2003). This occurs through a direct interaction of classical steroid receptors with proto-oncogenic tyrosine kinase (Src), the p85-regulatory subunit of Phosphatidylinositol 3-kinase (PI3K) and other signaling components. Activation of these pathways fosters cell cycle, prevents apoptosis and leads to cytoskeleton changes in reproductive as well as non reproductive cells.
The role of signaling activation in steroid action has been corroborated by findings showing that mouse embryo NIH3T3 fibroblasts express very low amount of classical androgen receptor (AR) which does not activate gene transcription. This receptor, through rapid and extra nuclear action, triggers migration upon stimulation with physiological concentrations (10nM) of the non aromatizable androgen, R1881 (Castoria et al. 2003).
By combining different approaches, it was observed that filamin A (FlnA) has an important role in androgen-stimulated migration.
In NIH3T3 cells, 10 nM R1881 rapidly induces interaction of AR with filamin A at cytoskeleton. AR/FlnA complex recruits and activates integrin beta1. Androgen assembled AR/FlnA/integrin beta1 complex activates both Ras-related C3 botulinum toxin substrate 1 (Rac1) and focal adhesion kinase (FAK), which independently of each other coordinate cytoskeletal changes and cell motility of fibroblasts.
Collected data indicate that AR/FlnA interaction in the extra-nuclear compartment of target cells plays a master role for the access of androgen to the signalling leading to cell migration. Such an interaction may impact human organ development as well as cancer progression and may offer new hints to gain a more tailored therapy of androgen-dependent human cancers.
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