Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A

被引：41

作者：

Wisnieski, Fernanda ^{[1
]}

Calcagno, Danielle Queiroz ^{[1
,5
]}

Leal, Mariana Ferreira ^{[1
,2
]}

Chen, Elizabeth Suchi ^{[1
]}

Gigek, Carolina Oliveira ^{[1
]}

Santos, Leonardo Caires ^{[1
]}

Pontes, Thais Brilhante ^{[1
]}

Rasmussen, Lucas Trevizani ^{[3
]}

Marques Payao, Spencer Luiz ^{[4
]}

Assumpcao, Paulo Pimentel ^{[5
]}

Lourenco, Laercio Gomes ^{[6
]}

Demachki, Samia ^{[5
]}

Artigiani, Ricardo ^{[7
]}

Burbano, Rommel Rodriguez ^{[8
]}

Smith, Marilia Cardoso ^{[1
]}

机构：

[1] Univ Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, BR-04023900 Sao Paulo, Brazil

[2] Univ Fed Sao Paulo, Dept Ortopedia & Traumatol, BR-04038032 Sao Paulo, Brazil

[3] Univ Sagrado Coracao, BR-17011160 Bauru, Brazil

[4] Fac Med Marilia, Dept Genet & Biol Mol, Hemoctr, BR-17519050 Marilia, Brazil

[5] Fed Univ Para, Nucleo Pesquisa Oncol, Hosp Joao de Barros Barreto, BR-66073000 Belem, Para, Brazil

[6] Univ Fed Sao Paulo, Disciplina Gastroenterol Cirurg, Dept Cirurgia, BR-04024002 Sao Paulo, Brazil

[7] Univ Fed Sao Paulo, Dept Patol, BR-04023000 Sao Paulo, Brazil

[8] Fed Univ Para, Lab Citogenet Humana, Inst Ciencias Biol, BR-66075110 Belem, Para, Brazil

来源：

TUMOR BIOLOGY | 2014年 / 35卷 / 07期

基金：

巴西圣保罗研究基金会;

关键词：

Gastric cancer; Acetylation; Histone acetyltransferase; Histone deacetylase; Gene expression; C-MYC AMPLIFICATION; NORTHERN BRAZIL; NUMERICAL ABERRATIONS; INDIVIDUALS; APOPTOSIS; PCAF; CHROMOSOME-8; INHIBITOR; CARCINOMA; INTERRELATIONSHIP;

D O I：

10.1007/s13277-014-1841-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gastric cancer is still the second leading cause of cancer-related death worldwide, even though its incidence and mortality have declined over the recent few decades. Epigenetic control using histone deacetylase inhibitors, such as trichostatin A (TSA), is a promising cancer therapy. This study aimed to assess the messenger RNA (mRNA) levels of three histone deacetylases (HDAC1, HDAC2, and HDAC3), two histone acetyltransferases (GCN5 and PCAF), and two possible targets of these histone modifiers (MYC and CDKN1A) in 50 matched pairs of gastric tumors and corresponding adjacent nontumors samples from patients with gastric adenocarcinoma, as well as their correlations and their possible associations with clinicopathological features. Additionally, we evaluated whether these genes are sensitive to TSA in gastric cancer cell lines. Our results demonstrated downregulation of HDAC1, PCAF, and CDKN1A in gastric tumors compared with adjacent nontumors (P < 0.05). On the other hand, upregulation of HDAC2, GCN5, and MYC was observed in gastric tumors compared with adjacent nontumors (P < 0.05). The mRNA level of MYC was correlated to HDAC3 and GCN5 (P < 0.05), whereas CDKN1A was correlated to HDAC1 and GCN5 (P < 0.05 and P < 0.01, respectively). In addition, the reduced expression of PCAF was associated with intestinal-type gastric cancer (P = 0.03) and TNM stages I/II (P = 0.01). The increased expression of GCN5 was associated with advanced stage gastric cancer (P = 0.02) and tumor invasion (P = 0.03). The gastric cell lines treated with TSA showed different patterns of histone deacetylase and acetyltransferase mRNA expression, downregulation of MYC, and upregulation of CDKN1A. Our findings suggest that alteration of histone modifier genes play an important role in gastric carcinogenesis, contributing to MYC and CDKN1A deregulation. In addition, all genes studied here are modulated by TSA, although this modulation appears to be dependent of the genetic background of the cell line.

引用

页码：6373 / 6381

页数：9

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