Carnitine palmitoyl transferase I (CPT1) catalyzes the transport of long-chain fatty acids into mitochondria for beta-oxidation. A link between CPT1 and apoptosis has been suggested on the basis of several experimental data. Nevertheless, results are contradictory about the effective role of CPT1 in cell survival control and cancer development. Conversely, Fatty acid synthase (FAS) enzyme, required for the synthesis of fatty acids, is found over-expressed in tumors and inhibition of FAS triggers apoptosis in human cancer cells. We have studied the tumor-specific modulation of CPT1 and FAS in human colorectal cancer (n = 11) and breast carcinomas (n = 24). CPT1 was significantly decreased in the cytoplasm of tumoral samples (p < or = 0.04), whereas FAS was increased (p < or = 0.04). A striking CPT1 nuclear localization was evident in the tumors (p < or = 0.04). In the nuclear environment the protein would modulate the levels of acetyl/acyl-CoA implicated in the regulation of gene transcription. At this purpose, we performed in vitro experiments using epithelial neoplastic (MCF-7, Caco-2, HepG2 cells) and non neoplastic cell lines (MCF-12F) confirming a nuclear localization of CPT1 protein exclusively in neoplastic cells. Moreover histone deacetylase (HDAC) activity showed significantly higher levels in nuclear extracts from neoplastic than from control cells. HDAC1 and CPT1 proteins coimmunoprecipitated in nuclear extracts from MCF-7 cells. The treatment with HDAC inhibitors such as trichostatin A and butyrate significantly decreased nuclear expression of CPT1 and its bond to HDAC1. We also identified the existence of CPT1A mRNA transcript variant 2 in MCF-7, beside to the classic isoform 1. The peculiar localization of CPT1 in the nuclei of human carcinomas and the disclosed functional link between nuclear CPT1 and HDAC1 propose a new role of CPT1 in the histonic acetylation level of tumors.
Mazzarelli, P., Pucci, S., Bonanno, E., Sesti, F., Calvani, M., & Spagnoli, L.g. (2007). Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation?. CANCER BIOLOGY & THERAPY, 6(10), 1606-1613.
|Tipologia:||Articolo su rivista|
|Citazione:||Mazzarelli, P., Pucci, S., Bonanno, E., Sesti, F., Calvani, M., & Spagnoli, L.g. (2007). Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation?. CANCER BIOLOGY & THERAPY, 6(10), 1606-1613.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/org/10.4161/cbt.6.10.4742|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||ott-2007|
|Titolo:||Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation?|
|Autori:||Mazzarelli, P; Pucci, S; Bonanno, E; Sesti, F; Calvani, M; Spagnoli, Lg|
|Appare nelle tipologie:||01 - Articolo su rivista|