A screen for genes that suppress loss of contact inhibition: Identification of
            <i>ING4</i>
            as a candidate tumor suppressor gene in human cancer

Kim, Suwon; Chin, Koei; Gray, Joe W.; Bishop, J. Michael

doi:10.1073/pnas.0407158101

Cited by 130 publications

(202 citation statements)

References 27 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: 55%

“…ING4, a novel member of the ING family, has recently emerged as a strong tumor suppressor gene that functions in cell proliferation, contact inhibition, and angiogenesis (Garkavtsev et al, 2004;Kim et al, 2004). ING4, along with ING5, was first isolated and characterized through a computational search of ING1 sequence homology .…”

mentioning

confidence: 99%

“…Previous studies demonstrated that overexpression of ING4 could induce a decreased cell population in the S phase of the cell cycle and apoptosis in a p53-dependent manner with increasing p21 expression in RKO cells . ING4 could also suppress the loss of contact inhibition elicited by MYCN or MYC (Kim et al, 2004), induce significant G2/M arrest of cell cycle, and enhance chemosensitivity to doxorubicin and etoposide in HepG2 cells (Zhang et al, 2004). Finally, ING4 could inhibit NF-kB activation by physically interacting with the p65 (RelA) subunit of nuclear factor NF-kB, resulting in transcriptional repression of the downstream NF-kBresponsive genes (such as IL-8, IL-6, COX-2, and CSF-3) and many angiogenesis-related genes, causing further inhibition of tumor angiogenesis (Garkavtsev et al, 2004).…”

mentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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: 55%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…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). ING4 was also isolated through a screening for genes able to suppress loss of contact inhibition without affecting cellular proliferation (Kim et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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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The new tumor suppressor genes ING: Genomic structure and status in cancer

Ythier

Larrieu

Brambilla

et al. 2008

Intl Journal of Cancer

115

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The Inhibitor of Growth 1 (ING1) gene has been identified and characterized as a Type-II tumor suppressor gene (TSG). Subsequently, 4 additional members of the family were identified by homology search. ING proteins contain a nuclear localization sequence (NLS) and a plant homeo domain (PHD) finger motif in their C-terminus. These proteins are involved in numerous signaling pathways especially in 2 tumor suppressor pathways: apoptosis and senescence. In human tumors, several studies have shown that the expression of ING1 is frequently lost or downregulated. It occurs most frequently at the RNA level, and thus epigenetics mechanism could be involved. We summarize the current knowledge on ING proteins functions and their involvement in various signaling pathways. We also review the studies that have investigated the ING protein status in human tumors. The interest of ING proteins as biomarkers and their role in tumor initiation and progression is discussed.

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A screen for genes that suppress loss of contact inhibition: Identification of ING4 as a candidate tumor suppressor gene in human cancer

Abstract: mycn ͉ proliferation ͉ cell transformation ͉ mutation ͉ breast cancer

Cited by 130 publications

References 27 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

The new tumor suppressor genes ING: Genomic structure and status in cancer

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