A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells

Hernandez, Maite; Shao, Qing; Yang, Xiang; Luh, Shi Ping; Kandouz, Mustapha; Batist, Gerald; Laird, Dale W.; Alaoui‐Jamali, Moulay A.

doi:10.1002/pros.20451

Cited by 45 publications

(31 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cx43 is an important factor of Cx, which not only has the function of Cx, but also is considered an anti-oncogene, whose decrease or loss of expression is closely related to tumor's genesis, development, and metastasis. Many tumor cells such as glioma, lung cancer, breast cancer, prostatic carcinoma show decreased or loss of Cx43 expression and the GJIC function [21,22]. Therefore, as a tumor suppressor, the expression of Cx43 can prompt malignant tumor's invasive degree and assesses the prognosis.…”

Section: Discussionmentioning

confidence: 98%

Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters

et al. 2009

View full text Add to dashboard Cite

Vasiformation is essential for the growth and metastasis of tumor. Vascular endothelial growth factor (VEGF) and connexin43 (Cx43) are important regulatory factors of vasiformation. This study aimed to find out the expression features of VEGF and Cx43 and their significance in pancreatic cancer. The expression levels of VEGF and Cx43 protein in the samples, which came from 100 patients of human pancreatic cancer tissues and adjacent normal pancreatic tissues, were examined by using immunohistochemical streptavidin-peroxidase (S-P) method, Western-blotting, and RT-PCR analyses. Compared with adjacent normal pancreatic tissues, RT-PCR showed that the expression of VEGF mRNA was significantly higher in pancreatic cancer tissues (0.788±0.290, P<0.01) and Cx43 mRNA was significantly lower in pancreatic cancer tissues (0.403±0.204, P<0.01). The expression of VEGF protein was higher in pancreatic cancer tissue (0.745±0.254, P<0.01) by Western-blot, and Cx43 protein was obviously lower in pancreatic cancer tissues (0.373±0.164, P<0.01). The immunohistochemical S-P method showed as follows: the positive expression rate of VEGF and Cx43 protein was 77 and 48% in pancreatic cancer tissues and 15 and 100% in adjacent normal pancreatic tissues; expressions of VEGF were related to tumor size, TNM stage, and lymph node metastasis (P<0.05); there was a close relation between the expression of Cx43 and histological grades, TNM stage, and lymph node metastasis (P<0.05). This present study suggests that VEGF is overexpressed and the expression of Cx43 is lower in pancreatic cancer. The expression of VEGF and Cx43 is significantly correlated with TNM stage and lymph node metastasis. Furthermore, VEGF and Cx43 may play an important role in the occurrence, development, and metastasis of pancreatic cancer. To examine VEGF and Cx43 may be of value in judging the malignancy degree and the prognosis of pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 98%

Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters

et al. 2009

View full text Add to dashboard Cite

show abstract

“…This strongly indicates a functional relevance of increased HDACs in prostate cancer rather than cancer epi-phenomenon. In addition, HDACs regulate expression of many genes known to participate in cancer invasion and metastasis, such as extracellular matrix (ECM), metastasis-associated proteins (MTAs), metastasis suppressor gene KAI1 and NF-κB, and AR function participating in hormone refractory development (30)(31)(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models

Gravina

Marampon²,

Giusti³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Histone deacetylase inhibitors (HDACi) are promising epigenetic cancer chemotherapeutics rapidly approaching clinical use. In this study, we tested using in vitro and in vivo models the differential biological effects of a novel HDAC inhibitor [belinostat (PXD101)], in a wide panel of androgensensitive and androgen-independent tumor cells. Belinostat significantly increased acetylation of histones H3 and H4. Belinostat potently inhibited the growth of prostate cancer cell lines (IC 50 range from 0.5 to 2.5 µM) with cytotoxic activity preferentially against tumor cells. This agent induced G 2 /M arrest and increased significantly the percentage of apoptosis mainly in androgen-sensitive tumor cells confirming its growthinhibitory effects. The cell death mechanisms were studied in three different prostate cancer cell lines with different androgen dependence and expression of androgen receptor; LAPC-4 and 22rv1 (androgen-dependent and expressing androgen receptor) and PC3 (androgen-independent not expressing androgen receptor). Belinostat induced the expression of p21 and p27, acetylation of p53 and G 2 /M arrest associated with Bcl2 and Bcl-Xl downmodulation and significant reduction of survivin, IAPs and Akt/pAkt and increased caspase-8 and -9 expression/activity. Belinostat effectiveness was dependent on the androgen receptor (AR), since the stable transfection of AR greatly increased the efficacy of this HDAC inhibitor. These observations were correlated using in vivo models. We demonstrated that belinostat preferentially resulted in antitumor effect in androgen-dependent tumor cells expressing AR. Our findings provide evidence that belinostat may be a promising anticancer drug for prostate cancer expressing AR, supporting its clinical role in prostate cancer.

show abstract

“…Recently, a HDAC-dependent mechanism was reported to be responsible for the transcriptional repression of Cx43 in prostate cancer cells, which affect Sp1 and Ap1 transcription factors together with the coactivator/adaptor p300/ CBP and possibly other factors to regulate Cx43 gene transcription. 29 . In addition, extracellular matrix protein fibronectin and overexpression of estrogen receptor-alpha gene has been shown to suppress the expression of Cx26 in alveolar epithelial cells and endometrial carcinoma cells, respectively.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation

et al. 2007

View full text Add to dashboard Cite

Summary Down-regulation of Cx43 expression had been shown to occur in nasopharyngeal carcinoma cells. The present study was undertaken to estimate if methylation of the promoter region in Cx43 gene was responsible for the repression of Cx43 expression in the CNE-1 nasopharyngeal carcinoma cells. Calcein transfer and lucifer yellow transfer were detected to evaluate gap junction intercellular communication (GJIC) in CNE-1 cells. It was found that the control CNE-1 cells showed no fluorescent dye transfer. After treatment with DNA methyltransferase inhibitor 5-aza-CdR, fluorescent dye transfer between cells became obvious. RT-PCR and Western blot were performed to determine the expression of Cx43 gene. The control CNE-1 cells showed a low expression level of Cx43, whereas 5-aza-CdR-treated CNE-1 cells showed an enhanced level of Cx43 expression. Methylation-sensitive restriction enzyme and PCR analysis showed that the methylation of the Cx43 gene promoter region occurred in CNE-1 cells. In addition, treatment with 5-aza-CdR inhibited the growth (including anchorage-independent growth) of CNE-1 cells, and resulted in an accumulation of cells in G0/G1 phase. These results indicate the promoter methylation as an important role in inactivation of Cx43 in CNE-1 cells.

show abstract

A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells

Abstract: Our results highlight the potential utility of inhibitors of HDAC to restore cx43 gene expression in prostate cancer.

Cited by 45 publications

References 60 publications

Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters

Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters

Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models

Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation

Contact Info

Product

Resources

About