Field defects in progression to gastrointestinal tract cancers

Bernstein, Carol; Bernstein, Harris; Payne, Claire M.; Dvorak, Katerina; Garewal, Harinder S.

doi:10.1016/j.canlet.2007.11.027

Cited by 57 publications

(49 citation statements)

References 61 publications

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“…Molecular abnormalities in colons harboring tumors are frequently widespread, with derangements in normal-appearing mucosa (43). To investigate more generalized “field effects”, we examined mRNA levels of several of the RAS components in distal colonic mucosa.…”

Section: Resultsmentioning

confidence: 99%

The Renin–Angiotensin System Mediates EGF Receptor–Vitamin D Receptor Cross-Talk in Colitis-Associated Colon Cancer

Dougherty

Mustafi

Sadiq

et al. 2014

Clinical Cancer Research

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Purpose We previously showed that epidermal growth factor receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D (VD) suppresses tumorigenesis. EGFR-vitamin D receptor (VDR) interactions, however, are incompletely understood. VD inhibits the renin-angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR-VDR cross-talk in colorectal carcinogenesis. Experimental Design To examine VDR-RAS interactions, we treated Vdr+/+ and Vdr/− mice with AOM/DSS. Effects of VDR on RAS and EGFR were examined by Westerns, immunostaining and real time PCR. We also examined the effect of vitamin D3 on colonic RAS in Vdr+/+ mice. EGFR regulation of VDR was examined in hypomorphic EgfrWaved2 (Wa2) and Egfrwildtype mice. Ang II-induced EGFR activation was studied in cell culture. Results Vdr deletion significantly increased tumorigenesis, activated EGFR and βcatenin signaling and increased colonic RAS components: including renin and angiotensin II. Dietary VD3 supplementation suppressed colonic renin. Renin was increased in human colon cancers. In studies in vitro, Ang II activated EGFR and stimulated colon cancer cell proliferation by an EGFR-mediated mechanism. Ang II also activated macrophages and colonic fibroblasts. Compared to tumors from EgfrWaved2 mice, tumors from Egfrwildtype mice showed up-regulated Snail1, a suppressor of VDR, and down-regulated VDR. Conclusions VDR suppresses the colonic RAS cascade, limits EGFR signals and inhibits colitis-associated tumorigenesis, whereas EGFR increases Snail1 and down-regulates VDR in colonic tumors. Taken together, these results uncover a RAS-dependent mechanism mediating EGFR and VDR cross-talk in colon cancer.

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Section: Resultsmentioning

confidence: 99%

The Renin–Angiotensin System Mediates EGF Receptor–Vitamin D Receptor Cross-Talk in Colitis-Associated Colon Cancer

Dougherty

Mustafi

Sadiq

et al. 2014

Clinical Cancer Research

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“…It has been postulated that BE begins with an initial expansion of metaplastic cells in response to CDKN2A inactivation [18][19][20]. These lesions are diploid or near diploid by flow cytometry and may not progress beyond this metaplastic state [21].…”

Section: Discussionmentioning

confidence: 99%

Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma

et al. 2012

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“…23 Epigenetic changes play a significant role in alteration of homeostasis of the epithelium, characterized by markedly enhanced proliferation, and development of cancer in normal adjacent tissue areas which are morphologically normal. 24 Secreted frizzled-related protein 1 (SFRP1) mRNA expression in normal adjacent tissue samples was higher than that from colorectal cancer samples. 25 When the crypts of normal adjacent tissue near the tumor site, the epithelial SFRP1 protein was decreased because of epigenetic silencing of the SFRP1 gene.…”

Section: Wnt Signalingmentioning

confidence: 99%

Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate writers

Farooqı¹,

Tang²,

Li³

et al. 2015

IJN

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Research concerning the epigenome over the years has systematically and sequentially shown substantial development and we have moved from global inhibition of modifications of the epigenome toward identification and targeted therapy against tumor-specific epigenetic mechanisms. In accordance with this approach, several drugs with epigenetically modulating activity have received considerable attention and appreciation, and recently emerging scientific evidence is uncovering details of their mode of action. High-throughput technologies have considerably improved our existing understanding of tumor suppressors, oncogenes, and signaling pathways that are key drivers of cancer. In this review, we summarize the general epigenetic mechanisms in cancer, including: the post-translational modification of DNA methyltransferase and its mediated inactivation of Ras association domain family 1 isoform A, Sonic hedgehog signaling, Wnt signaling, Notch signaling, transforming growth factor signaling, and natural products with epigenetic modification ability. Moreover, we introduce the importance of nanomedicine for delivery of natural products with modulating ability to epigenetic machinery in cancer cells. Such in-depth and comprehensive knowledge regarding epigenetic dysregulation will be helpful in the upcoming era of molecular genomic pathology for both detection and treatment of cancer. Epigenetic information will also be helpful when nanotherapy is used for epigenetic modification.

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Field defects in progression to gastrointestinal tract cancers

Cited by 57 publications

References 61 publications

The Renin–Angiotensin System Mediates EGF Receptor–Vitamin D Receptor Cross-Talk in Colitis-Associated Colon Cancer

The Renin–Angiotensin System Mediates EGF Receptor–Vitamin D Receptor Cross-Talk in Colitis-Associated Colon Cancer

Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma

Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate writers

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