Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

Wei, Lihui; Wu, Chunfu; Rajasekaran, Nirmal; Shin, Young Kee

doi:10.1159/000495956

Cited by 251 publications

(166 citation statements)

References 598 publications

(68 reference statements)

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“…Of note, only heterozygous carriers of protein-truncating variants were observed in our study conforming to the classical two-hit model for tumor suppressor genes [42,43]. No novel candidate genes within the DNA repair pathway were found in our study.…”

Section: Discussionsupporting

confidence: 74%

Inherited DNA Repair Gene Mutations in Men with Lethal Prostate Cancer

Rantapero

Wahlfors

Kähler

et al. 2020

Genes

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Germline variants in DNA repair genes are associated with aggressive prostate cancer (PrCa). The aim of this study was to characterize germline variants in DNA repair genes associated with lethal PrCa in Finnish and Swedish populations. Whole-exome sequencing was performed for 122 lethal and 60 unselected PrCa cases. Among the lethal cases, a total of 16 potentially damaging protein-truncating variants in DNA repair genes were identified in 15 men (12.3%). Mutations were found in six genes with CHEK2 (4.1%) and ATM (3.3%) being most frequently mutated. Overall, the carrier rate of truncating variants in DNA repair genes among men with lethal PrCa significantly exceeded the carrier rate of 0% in 60 unselected PrCa cases (p = 0.030), and the prevalence of 1.6% (p < 0.001) and 5.4% (p = 0.040) in Swedish and Finnish population controls from the Exome Aggregation Consortium. No significant difference in carrier rate of potentially damaging nonsynonymous single nucleotide variants between lethal and unselected PrCa cases was observed (p = 0.123). We confirm that DNA repair genes are strongly associated with lethal PrCa in Sweden and Finland and highlight the importance of population-specific assessment of variants contributing to PrCa aggressiveness.

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Section: Discussionsupporting

confidence: 74%

Inherited DNA Repair Gene Mutations in Men with Lethal Prostate Cancer

Rantapero

Wahlfors

Kähler

et al. 2020

Genes

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“…In recent years, with the development of economy and the change of lifestyle, the incidence of female BC in China has increased, and a trend for younger age at diagnosis has emerged (4)(5)(6). The occurrence of the majority of malignant tumors is associated with abnormal changes in certain key genes, such as inactivation of tumor suppressor genes, activation of oncogenes and abnormal expression of certain apoptosis-or proliferation-associated proteins (7,8). These changes lead to abnormal cell proliferation, apoptosis and differentiation.…”

Section: Introductionmentioning

confidence: 99%

miR‑200b regulates breast cancer cell proliferation and invasion by targeting radixin

Yuan¹,

Chu

Lu³

et al. 2020

Exp Ther Med

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Radixin is an important member of the Ezrin-Radixin-Moesin protein family that is involved in cell invasion, metastasis and movement. microRNA (miR)-200b is a well-studied microRNA associated with the development of multiple tumors. Previous bioinformatics analysis has demonstrated that miR-200b has a complementary binding site in the 3'-untranslated region of radixin mRNA. The present study aimed to investigate the role of miR-200b in regulating radixin expression, cell proliferation and invasion in breast cancer. Breast cancer tissues at different Tumor-Node-Metastasis (TNM) stages were collected; breast tissues from patients with hyperplasia were used as a control. miR-200b and radixin mRNA expression levels were tested by reverse transcription-quantitative PCR. Radixin protein expression was detected by western blotting. The highly metastatic MDA-MB-231 cells were divided into four groups and transfected with a miR-negative control (NC), miR-200b mimic, small interfering (si)RNA-NC or siRNA targeting radixin. Cell invasion was evaluated by Transwell assay and cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine staining. Compared with the control group, radixin mRNA expression was significantly higher in breast cancer tissues and increased with TNM stage. miR-200b expression levels exhibited the opposite trend. Radixin mRNA expression in breast cancer cells was notably higher, whereas miR-200b expression was lower compared with that in normal breast epithelial MCF-10A cells. The expression of radixin was higher, whereas miR-200b was lower in MDA-MB-231 cells compared with that in MCF-7 cells. miR-200b mimic or siRNA-radixin transfection downregulated the expression of radixin in MDA-MB-231 cells and attenuated the invasive and proliferative abilities of these cells. miR-200b-knockdown and radixin overexpression were associated with enhanced cell invasion in breast cancer. In conclusion, miR-200b regulates breast cancer cell proliferation and invasion by targeting radixin expression.

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“…defects, and potentiated by the action of cancerogenic substances. Two classes of genes have a key role in this process: proto-oncogenes and tumor suppressor genes, which are necessary for the control of proliferation, differentiation and cell death [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Expression of PCNA, CD-31 and HER-2 in Serbian patients with oral squamous cell carcinoma

Loncarevic

Brajković

Gardasevic

et al. 2019

ARCH BIOL SCI BELGRA

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Several studies have investigated the expression of tumor markers, including p53, HER-2, PCNA, EGFR, VEGFR CD-31 and Bcl-2 in patients with oral squamous carcinoma (OSC). This study aimed to determine the expression of proliferating cell nuclear antigen (PCNA), endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31) and human epidermal growth factor receptor-2 (HER-2) according to OSC stage. The prospective study included 62 patients diagnosed with OSC stages II and III. Surgical specimens were obtained from tumor and peritumoral tissues. We determined the pathohistological degree of tumor differentiation and the immunohistochemical expression of PCNA, CD-31 and HER-2 for each specimen. Immunohistochemical analysis of the expression of PCNA in tumor cells demonstrated poor staining of immunoreactive tumor cells in 23 patients (10 in stage II, 7 in stage IIIa and 6 in stage IIIb). Moderately expressed PCNA-immunoreactivity in the tumor cells in 17 patients (7 in stage II, 6 in stage IIIa and 4 in stage III), and extremely strong PCNA-immunoreactive staining in tumor cells of 10 patients with IIIb stage, was observed. These results suggest that PCNA expression combined with pathohistological findings could possess a prognostic value in determining the survival rates for patients with oral squamous cell carcinoma.

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Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

Cited by 251 publications

References 598 publications

Inherited DNA Repair Gene Mutations in Men with Lethal Prostate Cancer

Inherited DNA Repair Gene Mutations in Men with Lethal Prostate Cancer

miR‑200b regulates breast cancer cell proliferation and invasion by targeting radixin

Expression of PCNA, CD-31 and HER-2 in Serbian patients with oral squamous cell carcinoma

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