Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer

Abstract

Abstract. Epigenetic modifications play an important role during carcinogenesis. The main goal of this study was to examine expression levels of two critical enzymes, DNA methyltransferase-1 (DNMT1) and histone deacetylase-1 (HDAC1), by immunohistochemistry (IHC) in human pancreatic cancer and precancerous lesions: 20 foci containing normal ductal epithelial cells without an inflammatory background (DE), 30 containing ductal epithelial cells with an inflammatory background (DEI), 48 of pancreatic intraepithelial neoplasia-1A (PanIN-1A), 103 of PanIN-1B, 99 of PanIN-2, 30 of PanIN-3, 18 of intraductal papillary mucinous neoplasm A (IPMA), 10 of IPMB, 20 of IPMC, and 54 of pancreatic ductal adenocarcinoma (PDAC). The expression levels of both DNMT1 and HDAC1 increased from normal to precancerous lesions to pancreatic cancer, in a malignancydependent manner. Correlations between expression levels and clinicopathological features of the 54 PDAC patients were also analyzed. The expression of DNMT1 significantly correlated with nerve infiltration, degree of tumor differentiation and TNM staging (p<0.05), while that of HDAC1 correlated with proliferative activity, degree of tumor differentiation and TNM staging (p<0.05). Patients with higher expression of DNMT1 and/or HDAC1 had an overall lower survival than those with lower expression (p<0.05). Higher expression of DNMT1 and HDAC1 correlated with advanced stages of the disease and reflect the malignancy of pancreatic carcinoma. They may become new prognostic markers and potential therapeutic targets for pancreatic cancer.

DNA Methyltransferases: A Novel Target for Prevention and Therapy

“…In addition, they observed decreased levels of DNA methylation at candidate genes in the normal pancreas of DNMT1 hypomorphic mice (86). Moreover, the expression of DNMT1 protein increased with the development of pancreatic cancer from normal tissue to precancerous lesions (PanINs) and to cancer (PDAC) (106–109). Clinic pathological analyses by Wang and colleagues suggested that PDAC patients with higher DNMT1 protein expression had an overall lower survival rate than those with lower expression.…”

“…Clinic pathological analyses by Wang and colleagues suggested that PDAC patients with higher DNMT1 protein expression had an overall lower survival rate than those with lower expression. Moreover, higher DNMT1 expression correlated with advanced stages of the disease, reflecting the malignancy potential of PDAC (109). Recent studies examining DNMT mRNA expression in pancreatic cancer has also demonstrated that the levels of the three DNMTs increased with the development of pancreatic cancer from normal duct to pancreatic intraductal neoplasia and further to PDAC.…”

Emodin inhibits LOVO colorectal cancer cell proliferation via the regulation of the Bcl-2/Bax ratio and cytochrome c

“…Pharmacological studies have shown that emodin exhibits anticancer effects in a number of human cancers (3). In addition, previous studies have shown that emodin exerts antiproliferative and apoptosis-inducing effects on cell lines derived from ovarian (4) and lung (5) cancer and leukemia (6). However, at present there is little information demonstrating the possible antiproliferative effect of emodin on colorectal cancer.…”

Synthetic paclitaxel-octreotide conjugate reversing the resistance of A2780/Taxol to paclitaxel in xenografted tumor in nude mice

“…Fluctuation of microtubule composition expression may lead to dynamic changes in microtubule and eventually alter the tumor response to paclitaxel. The increased expression levels of α-tubulin and βIII-tubulin, mutation of βI-tubulin or down-regulation of microtubule associated proteins (MAPs) can undermine the inherent stability of microtubules and reduce the efficacy of paclitaxel [51–52]. In this study, decreased mRNA and protein expressions of α-tubulin and βIII-tubulin in tumor tissues were detected in each treatment group except the control group.…”