Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

Pradeep, Anamika; Sharma, Chandan; Sathyanarayana, Pradeep; Albanese, Chris; Fleming, John; Wang, Yichen; Wolfe, M. Michael; Baker, Kenneth M.; Pestell, Richard G.; Rana, Basabi

doi:10.1038/sj.onc.1207454

Cited by 96 publications

(80 citation statements)

References 63 publications

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“…Amplification or mutation of the cyclin D1 gene has not been reported in GC, although elevated cyclin D1 expression has been observed in ≈50% of GC cases (37). In GC, several factors are reportedly involved in cyclin D1 overexpression, including the RAF/MEK/ERK pathways (38), abrogation of TGF-β signaling (39), gastrin (40,41), Epstein-Barr virus (42), and H. pylori (43). However, the precise mechanism that regulates cyclin D1 expression in GC remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Hayakawa

Hirata

Nakagawa

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Mitogen-activated protein kinase (MAPK) pathways regulate multiple cellular functions and are highly active in many types of human cancers. Apoptosis signal-regulating kinase 1 (ASK1) is an upstream MAPK involved in apoptosis, inflammation, and carcinogenesis. This study investigated the role of ASK1 in the development of gastric cancer. In human gastric cancer specimens, we observed increased ASK1 expression, compared to nontumor epithelium. Using a chemically induced murine gastric tumorigenesis model, we observed increased tumor ASK1 expression, and ASK1 knockout mice had both fewer and smaller tumors than wild-type (WT) mice. ASK1 siRNA inhibited cell proliferation through the accumulation of cells in G1 phase of the cell cycle, and reduced cyclin D1 expression in gastric cancer cells, whereas these effects were uncommon in other cancer cells. ASK1 overexpression induced the transcription of cyclin D1, through AP-1 activation, and ASK1 levels were regulated by cyclin D1, via the Rb-E2F pathway. Exogenous ASK1 induced cyclin D1 expression, followed by elevated expression of endogenous ASK1. These results indicate an autoregulatory mechanism of ASK1 in the development of gastric cancer. Targeting this positive feedback loop, ASK1 may present a potential therapeutic target for the treatment of advanced gastric cancer. JNK | c-JunG astric cancer (GC) is a common cancer worldwide, associated with a high mortality despite its declining incidence in recent decades. Smoking, salted or smoked foods, and Helicobacter pylori appear to be major environmental inducers of GC (1-3). Although the role of H. pylori in causing mucosal effects has been investigated, which molecular signal(s) initiate the program of irreversible transformation remain unclear, and thus molecular targeting therapies for GC have not been well established.Mitogen-activated protein kinase (MAPK) pathways are important for the development of gastric tumorigenesis (4). Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed MAPK kinase kinase (MAP3K), activated by various stress stimuli, including reactive oxygen species (ROS), TNF-α, and LPS (5-7). ASK1 activates the JNK and p38 signaling pathways and is required for both oxidative stress and cytokine-induced apoptosis (5). Furthermore, ASK1 affects multiple cellular functions, including survival, differentiation, and the innate immune response (5,7,8) and has been reported to be involved in the pathogenesis of various human diseases, including neurodegenerative (9), cardiovascular (10), and inflammatory diseases (11,12). Additionally, ASK1 has been shown to participate in both colon (12) and skin (13) tumorigenesis through the regulation of inflammation and apoptosis. However, no reported study has demonstrated a role for ASK1 in gastric tumorigenesis.In this study, we examined the role of ASK1 in gastric tumorigenesis using both human GC samples and ASK1-deficient (ASK1 −/− ) mice. We demonstrated that ASK1 is important for gastric tumorigenesis through the regulation of cyclin D1 e...

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Section: Discussionmentioning

confidence: 99%

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Hayakawa

Hirata

Nakagawa

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Another possibility is simply the fact that every immortal cell line possesses slightly different characteristics that produce disparate results. For example, unlike AGS-B cells (Song et al, 2003b), in AGS-E cells, a related human gastric adenocarcinoma cell line overexpressing the gastrin receptor, G-17 induction of cyclin D1 transcription was mediated through both b-catenin and CREB pathways (Pradeep et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Gastrin stabilises β-catenin protein in mouse colorectal cancer cells

et al. 2005

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As gastrin may play a role in the pathophysiology of gastrointestinal (GI) malignancies, the elucidation of the mechanisms governing gastrin-induced proliferation has recently gained considerable interest. Several studies have reported that a large percentage of colorectal tumours overexpress or stabilise the b-catenin oncoprotein. We thus sought to determine whether gastrin might regulate b-catenin expression in colorectal tumour cells. Amidated gastrin-17 (G-17), one of the major circulating forms of gastrin, not only enhanced b-catenin protein expression, but also one of its target genes, cyclin D1. Furthermore, activation of b-catenin-dependent transcription by gastrin was confirmed by an increase in LEF-1 reporter activity, as well as enhanced cyclin D1 promoter activity. Finally, G-17 prolonged the t 1/2 of b-catenin protein, demonstrating that gastrin appears to exert its mitogenic effects on colorectal tumour cells, at least in part, by stabilising b-catenin.

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“…Although their binding sites are in close proximity, the direct interaction between CREB and b-catenin/TCF complex could not be detected, even in the presence of CBP/p300 (data not shown). The importance of the CRE has been reported in b-cateninmediated transcriptional activation of several other genes, such as cyclin D1 and WISP-1 (Xu et al, 2000;Pradeep et al, 2004).…”

Section: Suppression Of Cyclin D2 Expression By Ptenmentioning

confidence: 99%

GSK3β mediates suppression of cyclin D2 expression by tumor suppressor PTEN

Huang

et al. 2006

Oncogene

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PTEN, encoding a lipid phosphatase, is a tumor suppressor gene and is mutated in various types of cancers. It is reported to regulate G1 to S phase transition of the cell cycle by influencing the expression, protein stability and subcellular location of cyclin D1. Here, we provide evidence that PTEN modulates the transcription and protein stability of cyclin D2. Targeted deletion of Pten in mouse embryonic fibroblasts (MEFs) endowed cells with greater potential to overcome G1 arrest than wild-type MEFs and led to the elevated expression of cyclin D2, which was suppressed by the introduction of PTEN. We further defined a pathway involving GSK3b and b-catenin/TCF in PTEN-mediated suppression of cyclin D2 transcription. LiCl, an inhibitor of GSK3b, abolished inhibitory effect of PTEN on cyclin D2 expression, and TCF members could directly bind to the promoter of cyclin D2 and regulate its transcription in a CREB-dependent manner. Our results indicate that the downregulation of cyclin D2 expression by PTEN is mediated by the GSK3b/b-catenin/TCF pathway in cooperation with CREB, and suggest a convergence from the PI-3 kinase/PTEN pathway and the Wnt pathway in modulation of cyclin D2 expression.

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Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

Cited by 96 publications

References 63 publications

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Gastrin stabilises β-catenin protein in mouse colorectal cancer cells

GSK3β mediates suppression of cyclin D2 expression by tumor suppressor PTEN

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