A case of synchronous double primary breast carcinoma and osteosarcoma: Mismatch repair genes mutations as a possible cause for multiple early onset malignant tumors

Ahmed, H.; Salama, A.E.; Salem, Salem Eid; Bahnassy, Abeer A.

doi:10.12659/ajcr.883382

Cited by 8 publications

(10 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It forms a heterodimer with MSH6 or MSH3 to form the DNA repair complex. A previous study demonstrated that MSH2 promotes methylation, microsatellite instability and various mutational events associated with development of OS (42). It also distinguishes OS cancer stem cells from normal cells by mediating DNA repair (43).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Yang

Wang

2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. The aim of this study was to explore the underlying molecular mechanism related to the process and progression of osteosarcoma (OS). The differentially expressed genes (DEGs) were downloaded from the Gene Expression Omnibus database. The pathway and gene ontology (GO) enrichment analysis, as well as transcription factor, tumor-associated gene and tumor suppressor gene analyses were performed to investigate the functions of DEGs. Next, the protein-protein interaction (PPI) network was constructed and module analysis was further assessed by cluster analysis with the overlapping neighborhood expansion (Cluster ONE) cytoscape plug-in. A total of 359 upregulated and 614 downregulated DEGs were identified to be differentially expressed between OS samples and normal controls. Pathways significantly enriched by DEGs included the focal adhesion and chromosome maintenance pathways. Significant GO terms were cell adhesion, cell cycle and nucleic acid metabolic processes. The upregulated PPI network was constructed with 170 nodes and the downregulated PPI network was constructed with 332 nodes. Breast-ovarian cancer gene 1 (BRCA1), melanocyte-stimulating hormone 2 (MSH2), cyclin D1 (CCND1) and integrin α5 (ITGA5) were identified to be hub proteins in PPI. In conclusion, the dysregulated genes played key roles in the progression of OS. Cell adhesion is a significant biological process in OS development, and the genes BRCA1, MSH2, CCND1 and ITGA5 may be potential targets in the therapy of OS.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Yang

Wang

2016

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…It has been proven that upregulating cyclin D1 could suppress OS cell growth, metastasis, and apoptosis as an important signaling arm required for maximizing the mediator complex subunit 19 (Med19; Yu et al, 2014). There was a high expression of PCNA observed in the OS cell nucleus and cytoplasm (Wang, Luo, & Wang, 2006 (Ahmed et al, 2012). Another study has previously proven to us that c-myc could positively modulate MMR activity (Partlin et al, 2003).…”

Section: Discussionmentioning

confidence: 98%

“…More so, Jentzsch et al showed us that the MSH6 gene mutations could result in deficiencies in DNA MMR proteins (Jentzsch et al, ). Moreover, it has also been proven that a decreased expression of MSH6 is linked with longer OS cell survival times (Ahmed, Salama, Salem, & Bahnassy, ). Unfortunately, it is still unknown whether or not MSH6 gene silencing may have the same function with MSH6 genes mutations and whether it, when combined with DDP, will have the better inhibitory effect to OS cells.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of MSH6 gene silencing in combination with cisplatin on cell proliferation of human osteosarcoma cell line MG63

Liu

Zeng

Zhang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Osteosarcoma (OS) is one of the most common primary bone malignancies, with the survival rate of patients with OS remaining low. Therefore, we conducted this study to identify the potential role combination of both MSH6 gene silencing and cisplatin (DDP) plays in OS cell proliferation and apoptosis. Microarray‐based gene expression profiling was used to identify the differentially expressed genes (DEGs) in patients with OS, as well as microRNAs (miRNAs) that regulate the candidate gene. OS tissues from 67 patients with OS along with normal tissues from 24 amputee patients were collected for detection of the positive expression of mutS homolog 6 (MSH6) protein, mRNA, and protein expressions of c‐myc, cyclin D1, l‐2, B‐cell lymphoma 2 (Bcl‐2), Stathmin, proliferating cell nuclear antigen (PCNA), and Bcl‐2‐associated X (Bax). Moreover, after MSH6 silencing and DDP were treated on the selected human OS cell line MG63 with the highest expression of MSH6, cell viability, cell cycle distribution, and apoptosis were detected. The microarray analysis showed that MSH6 was upregulated in OS chip data. Furthermore, silencing MSH6 combined with DDP reduced expressions of c‐myc, cyclin D1, Bcl‐2, Stathmin, and PCNA, and elevated Bax expression, whereas inhibiting OS cell viability, impeding cell cycle distribution, and inducing apoptosis. In conclusion, our preliminary results indicated that the combination of MSH6 gene silencing coupled with DDP may have a better effect on the inhibition of OS cell proliferation and promote apoptosis, potentially providing targets for the OS treatment.

show abstract

“…Current opinions agree that the metastasis of osteosarcoma is a complex process involving multiple factors in a cascade, accompanying with the higher metastatic activity of tumor cells. Previous studies have indicated the participation of certain genes in the metastasis of osteosarcoma and named them osteosarcoma metastasis-related genes [ 18 – 20 ]. Therefore it is of critical values for the treatment against osteosarcoma to identify and confirm such genes, in addition to the functional characterization of their roles in the occurrence, progression and prognosis prediction [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

The Functional Role of PMP22 Gene in the Proliferation and Invasion of Osteosarcoma

Liu

Chen

2015

Med Sci Monit

View full text Add to dashboard Cite

BackgroundAs the most common primary bone tumor, osteosarcoma has an improved survival rates with advancement of treatment methods. A higher rate of metastasis, however, leads to the aggravation of the disease. Studies have shown that some genes, namely osteosarcoma metastasis-related genes, participate in the process of tumor metastasis. The peripheral myelin protein 22 (PMP22) gene has recently been found to be abundantly expressed in the oncogenesis of osteosarcoma. Its detailed role and function in the tumor metastasis, however, remains unknown.Material/MethodsThe recombinant retroviral plasmid pcDNA3.1-PMP22 was constructed and used to transfect osteosarcoma cells SOSP-M, whose cell proliferation was measured by MTT method. The formation of tumor cell colony, the cell migration and invasion were also measured. The signal transduction pathway MAPK was further analyzed by Western blotting.ResultsThe pcDNA3.1-PMP22 plasmid was confirmed to have a 305bp PMP22 fragment by EcoRI-XhoI dual digestion. Compared to the control group, osteosarcoma cell invasion was significantly facilitated by the transfection of pcDNA3.1-PMP22 plasmid (p<0.05). The recombinant plasmid also significantly potentiated the formation of tumor cell colony and increased the migration and invasion ability of tumor cells (p<0.05 in all cases). Phosphorylated p-ERK and p-P38 were also up-regulated by vector transfection (p<0.05).ConclusionsOsteosarcoma metastasis-related gene PMP22 participates in the proliferation, invasion, migration and colony formation of osteosarcoma cells possibly via the MAPK signal transduction pathway, providing evidences for further investigation of metastatic mechanism of osteosarcoma.

show abstract

A case of synchronous double primary breast carcinoma and osteosarcoma: Mismatch repair genes mutations as a possible cause for multiple early onset malignant tumors

Cited by 8 publications

References 16 publications

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Analysis of the molecular mechanism of osteosarcoma using a bioinformatics approach

Inhibitory effect of MSH6 gene silencing in combination with cisplatin on cell proliferation of human osteosarcoma cell line MG63

The Functional Role of PMP22 Gene in the Proliferation and Invasion of Osteosarcoma

Contact Info

Product

Resources

About