Hepatoid adenocarcinoma of the stomach

Inagawa, Satoshi; Shimazaki, Jun; Hori, Masao; Yoshimi, Fuyo; Adachi, Shinya; Kawamoto, Toru; Fukao, Katashi; Itabashi, Michio

doi:10.1007/s101200100016

Cited by 108 publications

(105 citation statements)

References 33 publications

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“…Dysfunction of the b-catenin degradation pathway results in aberrant accumulation of b-catenin; this is a frequent event in various human cancers, and the aberrant accumulation of b-catenin is reported to trigger oncogenesis and tumor progression (Chung, 2000;Lin et al, 2000;Park et al, 2001;Inagawa et al, 2002). However, it has also been shown that aberrant accumulation of b-catenin is not always accompanied by known dysfunction or mutation of the APC, Axin, or b-catenin genes.…”

Section: Discussionmentioning

confidence: 99%

“…Although aberrant accumulation of b-catenin is a frequent event observed in various human cancers including colorectal, lung, and breast cancers, hepatocellular carcinoma (HCC), and hepatoblastoma (Chung, 2000;Lin et al, 2000;Park et al, 2001;Inagawa et al, 2002), mutation of APC, Axin, or b-catenin is not commonly found in several human cancers including HCC (de La Coste et al, 1998). In fact, it has been reported that the b-catenin and Axin are mutated in only about 10 and 7% of HCC, respectively (Satoh et al, 2000;Devereux et al, 2001;Wong et al, 2001).…”

mentioning

confidence: 99%

“…These results indicate that the cytoplasmic accumulation of b-catenin is not associated with mutations in b-catenin, Axin, or APC in 35-80% of HCCs. Moreover, aberrant accumulation of b-catenin protein without any evidence of dysfunction in the GSK3b-mediated degradation pathway is not limited to HCCs (Chung, 2000;Lin et al, 2000;Park et al, 2001;Inagawa et al, 2002). Therefore, it is possible to hypothesize that dysfunction in the Siah-1-mediated degradation pathway may contribute to the accumulation of b-catenin in human cancers.…”

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confidence: 99%

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Siah-1L, a novel transcript variant belonging to the human Siah family of proteins, regulates β-catenin activity in a p53-dependent manner

et al. 2004

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b-Catenin is a potent oncogenic protein whose cytoplasmic accumulation is a frequent event in cancer cells. The level of b-catenin is regulated by two mechanisms: the adenomatous polyposis coli/Axin/glycogen synthase kinase 3b-dependent degradation pathway and the Siah-1/ Siah interacting protein/Ebi-mediated degradation pathway. In this study, we have investigated the functional significance of p53-inducible human Siah-family protein expression in the regulation of b-catenin activity. We show here by reverse-transcriptase polymerase chain reaction that two mRNA transcripts, designated human Siah-1 and Siah-1L, are generated from the human Siah-1 locus. Interestingly, the expression of Siah-1L was upregulated by p53, whereas human Siah-1 expression was constant. Furthermore, introduction of exogenous Siah-1L protein downregulated b-catenin protein and promoted apoptosis induced by anticancer drugs in cancer cells that lack endogenous p53. Thus, Siah-1L represents a new member of the human Siah family that is induced in response to p53 and plays an important role in the regulation of b-catenin activity in tumor cells. These findings also suggest new strategies for restoring tumor suppressive pathways lost in cancer cells that have suffered p53 inactivation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Siah-1L, a novel transcript variant belonging to the human Siah family of proteins, regulates β-catenin activity in a p53-dependent manner

et al. 2004

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“…It is also worth mentioning that several studies do not show a correlation between the nuclear accumulation of b-catenin and the expression of several canonical transcriptional targets in HCCs (e.g. cyclin D1; Inagawa et al, 2002;Joo et al, 2003;Prange et al, 2003). Thus, tumor-entity-specific expression pattern and differential protumorigenic molecular mechanisms of the Wnt pathway (e.g.…”

Section: Signaling Pathways and Their Dysregulationmentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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“…Cytoplasmic and/or nuclear accumulation of bcatenin is a highly frequent event affecting various cancers including colorectal, lung, breast, cervix cancers, melanoma, HCC and hepatoblastoma (Candidus et al, 1996;Rimm et al, 1999;Chung, 2000;Johnsson et al, 2000;Lin et al, 2000;Park et al, 2001;Shinohara et al, 2001;Ueda et al, 2001;Hommura et al, 2002;Inagawa et al, 2002). In colorectal cancers, b-catenin accumulation is often associated with mutational inactivation of APC gene, which affects almost 80% of these tumors .…”

Section: Introductionmentioning

confidence: 99%

p53 mutation as a source of aberrant β-catenin accumulation in cancer cells

Çağatay

Öztürk

2002

Oncogene

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b-catenin is involved in both cell -cell interactions and wnt pathway -dependent cell fate determination through its interactions with E-cadherin and TCF/LEF transcription factors, respectively. Cytoplasmic/nuclear levels of b-catenin are important in regulated transcriptional activation of TCF/LEF target genes. Normally, these levels are kept low by proteosomal degradation of bcatenin through Axin1-and APC-dependent phosphorylation by CKI and GSK-3b. Deregulation of b-catenin degradation results in its aberrant accumulation, often leading to cancer. Accordingly, aberrant accumulation of b-catenin is observed at high frequency in many cancers. This accumulation correlates with either mutational activation of CTNNB1 (b-catenin) or mutational inactivation of APC and Axin1 genes in some tumors. However, there are many tumors that display b-catenin accumulation in the absence of a mutation in these genes. Thus, there must be additional sources for aberrant bcatenin accumulation in cancer cells. Here, we provide experimental evidence that wild-type b-catenin accumulates in hepatocellular carcinoma (HCC) cells in association with mutational inactivation of p53 gene. We also show that worldwide p53 and b-catenin mutation rates are inversely correlated in HCC. These data suggest that inactivation of p53 is an important cause of aberrant accumulation of b-catenin in cancer cells.

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Hepatoid adenocarcinoma of the stomach

Cited by 108 publications

References 33 publications

Siah-1L, a novel transcript variant belonging to the human Siah family of proteins, regulates β-catenin activity in a p53-dependent manner

Siah-1L, a novel transcript variant belonging to the human Siah family of proteins, regulates β-catenin activity in a p53-dependent manner

Dysregulation of growth factor signaling in human hepatocellular carcinoma

p53 mutation as a source of aberrant β-catenin accumulation in cancer cells

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