http://www.cnr.it/ontology/cnr/individuo/prodotto/ID204955

Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer (Articolo in rivista) (literal)

Anno

2013-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1186/1471-2407-13-81 (literal)

Alternative label

Contino F, Mazzarella C, Ferro A, Lo Presti M, Roz E, Lupo C, Perconti G, Giallongo A, Feo (2013)
Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer
in BMC cancer (Online); Biomed Central Ltd., London (Regno Unito)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Contino F, Mazzarella C, Ferro A, Lo Presti M, Roz E, Lupo C, Perconti G, Giallongo A, Feo (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

13 (literal)

Rivista

BMC cancer (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

81 (literal)

Note

PubMe (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università di Palermo, Italy Istituto di Biomedicina e Immunologia Molecolare, CNR, Palermo, Italy Unità di Anatomia Patologica, Dipartimento Oncologico di III livello La Maddalena, Palermo, Italy (literal)

Titolo

Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer (literal)

Abstract

Backgound: The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far. Methods: To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry. Results: Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide -514 and - 262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples. Conclusions: Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC. (literal)

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