Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas

Gündüz, Mehmet; Nagatsuka, Hitoshi; Demircan, Kadir; Gündüz, Esra; Cengiz, Beyhan; Ouchida, Mamoru; Tsujigiwa, Hidetsugu; Yamachika, Eiki; Fukushima, Kunihiro; Beder, Levent Bekir; Hirohata, Satoshi; Ninomiya, Yoshifumi; Nishizaki, Kazunori; Shimizu, Kenji; Nagai, Noriyuki

doi:10.1016/j.gene.2005.02.014

Cited by 114 publications

(126 citation statements)

References 23 publications

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“…It is clear that ING4 has a markedly low-expression in many human malignant tumors, such as human gliomas, with the levels inversely correlated with the tumor grades (Garkavtsev et al, 2004), or shows a deletion such as in human breast cancer and squamous cell carcinomas (Kim et al, 2004;Gunduz et al, 2005). In the present study, we showed that the expression of ING4 was markedly reduced in lung adenocarcinoma by RT-PCR as compared with normal lung tissues.…”

Section: Discussionsupporting

confidence: 56%

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Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt‐1/β‐Catenin Signaling Pathway

Li¹,

Cai²,

Liang³

et al. 2008

The Anatomical Record

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ING4, as a novel candidate tumor suppressor gene, has been implicated in several human malignances by tumor growth inhibition and apoptosis enhancement. The mechanism of ING4 remains largely unknown. The purpose of this study was to investigate the inhibitory tumor growth effects of ING4 on lung adenocarcinoma, and its mechanism, by ING4 cDNA transduction into A549 cells. Furthermore, the expression level of ING4 in lung adenocarcinoma tissues was examined. The expression of ING4 was markedly reduced in human lung adenocarcinoma tissues. Overexpression of ING4 can induce growth inhibition in A549 cells both in vitro and in vivo, and also induce up-regulation of p27, down-regulation of cyclinD1, SKP2, and Cox2, and inactivation of the Wnt-1/b-catenin pathway. Moreover, overexpression of ING4 can enhance the sensitivity of A549 cells to radiotherapy and chemotherapy. Thus, ING4 may play an inhibitory role on A549 cell proliferation and tumor growth in lung adenocarcinoma by up-regulation or down-regulation of cell proliferation-regulating proteins such as p27, cyclinD1, SKP2, and Cox2 by means of inactivation of Wnt-1/b-catenin signaling.

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Section: Discussionsupporting

confidence: 56%

“…ING4, as a novel candidate tumor suppressor gene, has been implicated in several human malignancies such as gliomas, breast tumors, and squamous cell carcinomas (Garkavtsev et al, 2004;Kim et al, 2004;Gunduz et al, 2005). It also plays a role in negatively regulating tumor growth and apoptosis.…”

mentioning

confidence: 99%

Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt‐1/β‐Catenin Signaling Pathway

Li¹,

Cai²,

Liang³

et al. 2008

The Anatomical Record

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show abstract

“…A large body of evidence documents ING4 involvement in human cancer through different mechanisms. Loss of heterozygosity has been reported in head and neck squamous cell carcinomas and in breast tumors (Kim et al, 2004;Gunduz et al, 2005). ING4 was found downregulated in gliomas and the extent of downregulation correlated with level of malignancy (Garkavtsev et al, 2004).…”

Section: Discussionmentioning

confidence: 93%

“…The ING4 gene, located at chromosome 12p13.31, consists of eight exons and encodes a 29-kDa protein expressed in multiple human tissues (Garkavtsev et al, 2004;Gunduz et al, 2005;He et al, 2005). Allelic loss of ING4 locus has been reported in head and neck squamous cell carcinomas and in breast tumors (Kim et al, 2004;Gunduz et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

et al. 2007

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Inhibitor of growth (ING)4, member of a gene family encoding potential tumor suppressors, is implicated as a repressor of angiogenesis and tumor growth and suppresses loss of contact inhibition in vitro. Here, we report that ING4 undergoes alternative splicing. Expression analysis identified novel ING4 spliced variant mRNAs encoding proteins devoid of different portions. The ING4 variants were detected in both normal and tumor tissues. The existence of ING4 variants was confirmed by several approaches, including reverse transcriptase-polymerase chain reaction, real-time PCR and in silico experiments. To investigate the functional consequences of alternative splicing the ING4 variant cDNAs were expressed in mammalian cells. Our studies indicated that (i) the ING4 variants do not differ from wild-type in their nuclear localization, interaction with p53 and association to HBO1 complex; and (ii) the ING4-DEx6A variant, devoid of the C-terminal portion, loses the capability to inhibit NF-jB. On the whole our data suggest that alternative splicing could modulate the activity of ING4 tumor suppressor protein.

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Duplication 12p and Pallister–Killian syndrome: A case report and review of the literature toward defining a Pallister–Killian syndrome minimal critical region

Izumi

Conlin

Berrodin

et al. 2012

American J of Med Genetics Pt A

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Pallister-Killian syndrome (PKS) is a multisystem sporadic genetic condition characterized by facial anomalies, variable developmental delay and intellectual impairment, hypotonia, hearing loss, seizures, pigmentary skin differences, temporal alopecia, diaphragmatic hernia, congenital heart defects, and other systemic abnormalities. PKS is typically caused by the presence of a supernumerary isochromosome composed of the short arms of chromosome 12 resulting in tetrasomy 12p, which is often present in a tissue limited mosaic state. The PKS phenotype has also often been observed in individuals with complete or partial duplications of 12p (trisomy 12p rather than tetrasomy 12p) as the result of an interstitial duplication or unbalanced translocation. We have identified a proposita with PKS who has two small de novo interstitial duplications of 12p which, along with a review of previously reported cases, has allowed us to define a minimum critical region for PKS.

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Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas

Cited by 114 publications

References 23 publications

Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt‐1/β‐Catenin Signaling Pathway

Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt‐1/β‐Catenin Signaling Pathway

Detection of novel mRNA splice variants of human ING4 tumor suppressor gene

Duplication 12p and Pallister–Killian syndrome: A case report and review of the literature toward defining a Pallister–Killian syndrome minimal critical region

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