Disease relevance of ING1

• Here we analyzed expression profiles in mouse mammary epithelial cells (NMuMG) by using a cDNA microarray consisting of 2304 mouse cDNAs after inducing transformation with antisense inhibitor of growth 1 (ING1) in retrovirus vector [1].
• Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors [2].
• In tumor samples, ING1 proteins aberrantly localized to the cytoplasm, and to a lesser extent, to the nucleus of glioma cells [2].
• CONCLUSIONS: Our data indicate that although mutations of ING1 seem to be infrequent in human brain tumors, deregulated expression and mislocalization of ING1 proteins, particularly the p33ING1b isoform, are common events in gliomas and glioblastomas [2].
• Mutations of the ING1 tumor suppressor gene detected in human melanoma abrogate nucleotide excision repair [3].

High impact information on ING1

• Limited analyses of tumour cell lines show that mutation of the ING1 gene occurs in neuroblastoma cells and reduced expression was seen in some breast cancer cell lines [4].
• Acute expression of transfected constructs encoding this gene inhibited cell growth while chronic expression of ING1 antisense constructs promoted cell transformation [4].
• These results demonstrate that ING1 can act as a potent growth regulator in normal and in established cells and provide evidence for a role as a candidate tumour suppressor gene whose inactivation may contribute to the development of cancers [4].
• The properties of p33ING1 suggest its involvement in the negative regulation of cell proliferation and in the control of cellular ageing, anchorage dependence and apoptosis [5].
• ING1 promotes DNA repair and interacts with proliferating cell nuclear antigen, thus linking DNA repair, apoptosis and chromatin remodelling [6].

Chemical compound and disease context of ING1

• Potential new probiotic strains Lactobacillus brevis PELI, L. reuteri ING1, L. rhamnosus VTT E-800 and L. rhamnosus LC-705 were assessed for their adhesion properties using the human intestinal mucus model [7].
• MATERIALS AND METHODS: Various malignant brain tumor cell lines were examined for their sensitivity to cisplatin, doxorubicin, etoposide and the antimitotic agents vincristine and paclitaxel by MTT-cytotoxicity assays. p33ING1 mRNA expression was determined by RT-PCR [8].

Biological context of ING1

• Together with the finding that human ING1 proteins bind PCNA in a DNA damage-dependent manner, these data suggest that ING1 proteins provide a direct linkage between DNA repair, apoptosis, and chromatin remodeling via multiple HAT.ING1.PCNA protein complexes [9].
• Human ING1 proteins differentially regulate histone acetylation [9].
• These data indicate that ING1 competitively binds PCNA through a site used by growth regulatory and DNA damage proteins, and may contribute to regulating the switch from DNA replication to DNA repair by altering the composition of the PCNA protein complex [10].
• It is very likely that, by linking DNA repair, apoptosis and chromatin remodeling to the transcriptional regulation of critical genes, ING1 exerts it tumor suppressor functions by helping maintain genomic stability [11].
• We show that 20% of the melanoma primaries contained missense mutations in the SAP30-interacting domain and PHD finger motif of the ING1 gene with the R102L and N260S alterations observed more than once [3].

Anatomical context of ING1

• Here we present the first report of ING1 expression and mutation analyses in human brain tumor samples and malignant glioma cell lines [2].
• Chronic expression of antisense ING1 RNA reproducibly resulted in extension of the proliferative life span of normal human fibroblasts by approximately seven population doublings [12].
• UV induction of ING1 in keratinocytes suggests that ING1 may play a role in cellular stress response and skin carcinogenesis [13].
• Reduced expression of the two major alternatively spliced ING1 messenger RNA variants, p47(ING1a) and p33(ING1b) was variable, but was reduced (1.2-10-fold) in 12 of 19 AdEGJs compared to normal esophageal epithelium [14].
• We found decreased expression of ING1 mRNA in 4 of 5 T-cell lines and 5 of 11 B-cell lines including two Burkitt lymphomas and two myelomas [15].

Associations of ING1 with chemical compounds

• Elevated expression of ING1 in P19 and rodent fibroblast cells containing a tetracycline-controlled human c-myc gene enhanced the extent of serum starvation-induced apoptosis [16].
• The family of proteins inhibitors of growth (ING) contains a PHD finger that bind to histone-3 trimethylated at lysine 4, and those of ING1 and ING2 also act as nuclear phosphoinositide receptors [17].
• Bisulfite sequencing results confirmed the p33ING1b promoter methylation status of these methylation positive cases [18].
• Results from the sulforhodamine B cell survival assay and flow cytometry analysis show no significant difference among cells transfected with vector, p33ING1, and antisense p33ING1 [19].
• These results showed that p33ING1b enhanced estrogen-induced ER alpha activity through the AF2 domain [20].

Physical interactions of ING1

• ING1 represses transcription by direct DNA binding and through effects on p53 [21].
• The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b [22].

Regulatory relationships of ING1

• Recently, a potential tumour suppressor gene ING1 (inhibitor of growth 1) was shown to inhibit cell growth and induce apoptosis in the presence of p53 [23].

Other interactions of ING1

• We have identified p33ING1b, a negative growth regulator involved in the p53 pathway, as a SAP30-associated protein [24].
• Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex [25].
• UV-induced binding of ING1 to PCNA regulates the induction of apoptosis [10].
• Furthermore, a novel gene, designated as ING2, sharing 76% nucleotide homology with ING1 was identified in the breast cancer cDNA library [26].
• We previously showed two members of the ING family, ING1 and ING3 as a tumor suppressor gene in head and neck cancer [27].

Analytical, diagnostic and therapeutic context of ING1

• Indeed, electrophoretic mobility shift assays confirmed that HNF1 binds to AT-motifs, but we found, surprisingly, that the ING1 complexes binding to these AT-motifs were devoid of HNF1 protein [21].
• The host-cell-reactivation assay and radioimmunoassay were used to determine the role of ING1 mutations in nucleotide excision repair [3].
• We examined the expression of ING1 mRNA in breast cancer cell lines and clinical breast cancer tissues, using quantitative RT-PCR and real time TaqMan technology [28].
• Immunohistochemistry, single-strand conformation polymorphism, and DNA sequencing were used to determine the expression and mutational status of the ING1 gene in 54 basal cell carcinoma biopsies [29].
• Polymerase chain reaction (PCR)-based assays were used to characterize ING1 and p53 alterations, relative to histologically normal esophageal mucosa [14].

References