Expression of tumor suppressor gene ING4 in ovarian carcinoma is correlated with microvessel density

Liu, Yinglan; Yu, Liqian; Wang, Yingwei; Zhang, Yaling; Wang, Yingchao; Zhang, Guangmei

doi:10.1007/s00432-011-1099-5

Cited by 25 publications

(18 citation statements)

References 38 publications

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“…Loss of ING proteins was generally found to correlate with cancer progression [22-25] and inhibiting the function of ING1 in chromatin modification by cytoplasmic localization, also positively correlated with tumor progression in head and neck cancers [22]. ING4 inhibited invasion and migration in a melanoma cell model in vitro [23] while ING1 and ING4 were reported to inhibit angiogenesis in glioblastoma [26, 27] and to negatively correlate with microvessel density in ovarian cancers [28]. ING1 was also reported to be a target of miR-622, which inhibits cell migration and invasion [29].…”

Section: Introductionmentioning

confidence: 99%

Reduced ING1 levels in breast cancer promotes metastasis

et al. 2014

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INhibitor of Growth 1 (ING1) expression is repressed in breast carcinomas, but its role in breast cancer development and metastasis is unknown. ING1 levels were quantified in >500 patient samples using automated quantitative fluorescence immunohistochemistry, and data were analysed for correlations to patient outcome. Effects of altering ING levels were examined in microarrays and metastasis assays in vitro, and in a mouse metastasis model in vivo. ING1 levels were lower in tumors compared to adjacent normal breast tissue and correlated with tumor size (p=0.019) and distant recurrence (p=0.001) in ER- or Her2+ patients. In these patients ING1 predicted disease-specific and distant metastasis-free survival. Transcriptome analysis showed that the pathway most affected by ING1 was breast cancer (p = 0.0008). Decreasing levels of ING1 increased, and increasing levels decreased, migration and invasion of MDA-MB231 cells in vitro. ING1 overexpression also blocked cancer cell metastasis in vivo and eliminated tumor-induced mortality in mouse models. Our data show that ING1 protein levels are downregulated in breast cancer and for the first time, we show that altering their levels regulates metastasis in vitro and in vivo, which indicates that ING1 may have a therapeutic role for inhibiting metastasis of breast cancer.

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Section: Introductionmentioning

confidence: 99%

Reduced ING1 levels in breast cancer promotes metastasis

et al. 2014

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“…The correlation between ING4 and angiogenesis has been further confirmed in various cancers including ovarian cancer, colon cancer and breast cancer [74][75][76][77]. These functions depended on the interaction between ING4 and the nuclear factor NF-κB in glioblastoma cells.…”

Section: Angiogenesismentioning

confidence: 79%

The Emerging Role of Inhibitor of Growth 4 as a Tumor Suppressor in Multiple Human Cancers

Cui

Gao

Zhang

et al. 2015

Cell Physiol Biochem

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Inhibitor of growth 4 (ING4), a member of the conserved ING family, has been identified as an important tumor suppressor since it plays a critical role in the regulation of chromatin modification, cell proliferation, angiogenesis and cell migration. Some observations suggest that ING4 acts as a key regulator of tumorigenesis through modifying gene transcription in part by regulating the transcription factors p53 and NF-kappaB (NF-κB). However, these models have yet to be substantiated by further investigations. Numerous reports describe the reduced expression of ING4 in cancers, and the responsible mechanisms are involved in gene deletion, mutation, transcriptional and post-transcriptional dysregulation. This review aims to summarize the recent published literature that investigates the role of ING4 in regulating tumorigenesis and progression, and explore its potential for cancer treatment.

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“…Instead, it was noted that the degree of reduction in ING4 expression correlated with the progression from low to high grades of osteosarcoma, according to the Enneking classification system for malignant bone tumors (P=0.002). ING4, a novel tumor suppressor of the ING family, has potential tumor-suppressing effects that are exerted through various signaling pathways, including tumorigenesis, cell cycle regulation, angiogenesis, cell apoptosis, DNA repair, migration and transcriptional regulation (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(37)(38)(39)(40)(41)(42)(43). These functions of ING4, which acts as an oncogene suppressor in numerous tumor types, have been identified repeatedly in vitro and in vivo (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(37)(38)…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of NF-κB negatively regulates various target genes, including matrix metalloproteinase (MMP)-2, MMP-9, interleukin (IL)-6, IL-8, cyclooxygenase-2 and colony stimulating factor-3. The downregulation of these cytokines inhibits angiogenesis and tumor cell growth (11)(12)(13)(14)(15). In RKO colorectal cancer cells, ING4 expression was able to decrease the cell population in the S-phase of the cell cycle in a p53-dependent manner, as well as upregulate p21 expression (16).…”

Section: Introductionmentioning

confidence: 99%

Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

et al. 2016

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Abstract. Osteosarcoma is the most prevalent type of primary malignant bone tumor. Inhibitor of growth 4 (ING4) has been demonstrated to function as a tumor suppressor through multiple pathways, and is its expression is understood to be suppressed or reduced in various malignancies. The present study aimed to investigate the expression of ING4 and to determine its prognostic value in osteosarcoma tissue. Formalin-fixed, paraffin-embedded tissue microarrays were analyzed, and contained 41 osteosarcoma specimens and 11 normal bone tissue specimens with duplicate cores. ING4 expression was evaluated by immunohistochemical staining. The association between ING4 expression in the osteosarcoma and normal bone tissues was analyzed, in addition to the association between ING4 expression and Enneking classification of the osteosarcoma tissues. A significant statistical difference was observed in the ING4 immunohistochemical staining score between the osteosarcoma and normal bone tissues (P<0.001). Furthermore, a significant negative correlation was detected between the ING4 immunohistochemical staining scores and the Enneking classification results of the 41 osteosarcoma tissues (P=0.002). Low expression of ING4 was observed in the osteosarcoma specimens, and this reduced expression of ING4 was negatively correlated with Enneking classification. Thus, the results of the present study indicate that ING4 may serve as a promising prognostic marker in osteosarcoma. IntroductionOsteosarcoma, the most common primary bone malignancy, accounts for ~20% of all bone tumors and ~5% of all pediatric tumors (1). Osteosarcoma has an overwhelming tendency for invasion and early metastasis (2). Although treatment with surgery and neoadjuvant chemotherapy appears to cure 60-70% of cases (3), the 5-year survival rate for patients with recurrent and metastatic osteosarcoma is only 20% (4,5). Research investigating the mechanism of osteosarcoma development has primarily focused on chromosomal abnormalities, genetic alterations of tumor suppressor genes, activation of oncogenes and dysregulation of major signaling pathways. However, the molecular events that lead to the development of osteosarcoma are not yet fully understood.Inhibitor of growth 4 (ING4) functions as a tumor suppressor, thus serving an inhibitory role during the generation and development of various types of tumor, including thyroid (6), gastric (7), lung (8) and breast cancer (9). ING4 physically interacts with and phosphorylates p65, a subunit of nuclear factor-κB (NF-κB), therefore suppressing the activity of NF-κB (10). The inhibition of NF-κB negatively regulates various target genes, including matrix metalloproteinase (MMP)-2, MMP-9, interleukin (IL)-6, IL-8, cyclooxygenase-2 and colony stimulating factor-3. The downregulation of these cytokines inhibits angiogenesis and tumor cell growth (11-15). In RKO colorectal cancer cells, ING4 expression was able to decrease the cell population in the S-phase of the cell cycle in a p53-dependent manner, as well as upregulate p21...

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Expression of tumor suppressor gene ING4 in ovarian carcinoma is correlated with microvessel density

Abstract: Loss of ING4 may promote microvessel formation and plays a role in facilitating the development of ovarian cancer. Although the specific mechanisms are not yet understood, our data suggest that ING4 may be a promising target for the treatment for ovarian cancer.

Cited by 25 publications

References 38 publications

Reduced ING1 levels in breast cancer promotes metastasis

Reduced ING1 levels in breast cancer promotes metastasis

The Emerging Role of Inhibitor of Growth 4 as a Tumor Suppressor in Multiple Human Cancers

Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

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