scholarly journals Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Huili Li ◽  
Jiliang Wang ◽  
Kun Huang ◽  
Tao Zhang ◽  
Lu Gao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Expression Pattern ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Transcriptional Coactivator ◽  
Wild Type ◽  
Mutational Status ◽  
Sw480 Cells

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, in vitro and in vivo tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1 expression.

Expression of wild-type p53 is not compatible with continued growth of p53-negative tumor cells

1991 ◽  
Vol 11 (1) ◽  
pp. 1-11
Author(s):  
P Johnson ◽  
D Gray ◽  
M Mowat ◽  
S Benchimol
Keyword(s):  
Tumor Suppressor ◽  
Tumor Cell ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Tumor Cell Lines ◽  
Wild Type ◽  
Wild Type P53 ◽  
Negative Tumor

Inactivation of the cellular p53 gene is a common feature of Friend virus-induced murine erythroleukemia cell lines and may represent a necessary step in the progression of this disease. As well, frequent loss or mutation of p53 alleles in diverse human tumors is consistent with the view of p53 as a tumor suppressor gene. To examine the significance of p53 gene inactivation in tumorigenesis, we have attempted to express transfected wild-type p53 in three p53-negative tumor cell lines: murine DP16-1 Friend erythroleukemia cells, human K562 cells, and SKOV-3 cells. We found that aberrant p53 proteins, which differ from wild-type p53 by a single amino acid substitution, were expressed stably in these cells, whereas wild-type p53 expression was not tolerated. The inability of p53-negative tumor cell lines to support long-term expression of wild-type p53 protein is consistent with the view that p53 is a tumor suppressor gene.

scholarly journals Expression of wild-type p53 is not compatible with continued growth of p53-negative tumor cells.

1991 ◽  
Vol 11 (1) ◽  
pp. 1-11 ◽  
Author(s):  
P Johnson ◽  
D Gray ◽  
M Mowat ◽  
S Benchimol
Keyword(s):  
Tumor Suppressor ◽  
Tumor Cell ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Tumor Cell Lines ◽  
Wild Type ◽  
Wild Type P53 ◽  
Negative Tumor

Inactivation of the cellular p53 gene is a common feature of Friend virus-induced murine erythroleukemia cell lines and may represent a necessary step in the progression of this disease. As well, frequent loss or mutation of p53 alleles in diverse human tumors is consistent with the view of p53 as a tumor suppressor gene. To examine the significance of p53 gene inactivation in tumorigenesis, we have attempted to express transfected wild-type p53 in three p53-negative tumor cell lines: murine DP16-1 Friend erythroleukemia cells, human K562 cells, and SKOV-3 cells. We found that aberrant p53 proteins, which differ from wild-type p53 by a single amino acid substitution, were expressed stably in these cells, whereas wild-type p53 expression was not tolerated. The inability of p53-negative tumor cell lines to support long-term expression of wild-type p53 protein is consistent with the view that p53 is a tumor suppressor gene.

Codeletion of theJUN proto-oncogene and theCDKN2A tumor-suppressor gene inHRAS-transformed rat embryo fibroblast cell lines

1997 ◽  
Vol 20 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Jian-Nian Zhou ◽  
Sofia Ljungdahl ◽  
Dan Röhme ◽  
Göran Levan ◽  
Maria C. Shoshan ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
Suppressor Gene ◽  
Rat Embryo ◽  
Fibroblast Cell Lines

Mutations in tumor suppressor gene, FBXW7, are associated with carboplatin resistance in endometrial cancer cell lines

2015 ◽  
Vol 139 (1) ◽  
pp. 194 ◽  
Author(s):  
Alexandre Buckley de Meritens ◽  
Ayesha Joshi ◽  
Christopher Miller ◽  
Lora Hedrick Ellenson ◽  
Divya Gupta
Keyword(s):  
Endometrial Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Suppressor Gene ◽  
Endometrial Cancer Cell

scholarly journals NDST4 Is a Novel Candidate Tumor Suppressor Gene at Chromosome 4q26 and Its Genetic Loss Predicts Adverse Prognosis in Colorectal Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67040 ◽  
Author(s):  
Sheng-Tai Tzeng ◽  
Ming-Hong Tsai ◽  
Chi-Long Chen ◽  
Jing-Xing Lee ◽  
Tzu-Ming Jao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Candidate Tumor Suppressor ◽  
Candidate Tumor Suppressor Gene

scholarly journals GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor‐suppressor gene TGFβR2 in colorectal cancer

2019 ◽  
Vol 111 (2) ◽  
pp. 343-355 ◽  
Author(s):  
Sho Nambara ◽  
Takaaki Masuda ◽  
Yuta Kobayashi ◽  
Kuniaki Sato ◽  
Taro Tobo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Chromosome 7

scholarly journals Functional evidence for a second tumor suppressor gene on human chromosome 17

1994 ◽  
Vol 14 (1) ◽  
pp. 534-542
Author(s):  
P Chen ◽  
N Ellmore ◽  
B E Weissman
Keyword(s):  
Tumor Suppressor ◽  
Cell Line ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Chromosome 17 ◽  
Hybrid Cells ◽  
Tumorigenic Potential ◽  
Normal Human ◽  
Second Tumor

The development and progression of human tumors often involves inactivation of tumor suppressor gene function. Observations that specific chromosome deletions correlate with distinct groups of cancer suggest that some types of tumors may share common defective tumor suppressor genes. In support of this notion, our initial studies showed that four human carcinoma cell lines belong to the same complementation group for tumorigenic potential. In this investigation, we have extended these studies to six human soft tissue sarcoma cell lines. Our data showed that hybrid cells between a peripheral neuroepithelioma (PNET) cell line and normal human fibroblasts or HeLa cells were nontumorigenic. However, hybrid cells between the PNET cell line and five other soft tissue sarcoma cell lines remained highly tumorigenic, suggesting at least one common genetic defect in the control of tumorigenic potential in these cells. To determine the location of this common tumor suppressor gene, we examined biochemical and molecular polymorphic markers in matched pairs of tumorigenic and nontumorigenic hybrid cells between the PNET cell line and a normal human fibroblast. The data showed that loss of the fibroblast-derived chromosome 17 correlated with the conversion from nontumorigenic to tumorigenic cells. Transfer of two different chromosome 17s containing a mutant form of the p53 gene into the PNET cell line caused suppression of tumorigenic potential, implying the presence of a second tumor suppressor gene on chromosome 17.

scholarly journals Facile profiling of molecular heterogeneity by microfluidic digital melt

2018 ◽  
Vol 4 (9) ◽  
pp. eaat6459 ◽  
Author(s):  
Christine M. O’Keefe ◽  
Thomas R. Pisanic ◽  
Helena Zec ◽  
Michael J. Overman ◽  
James G. Herman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Single Molecule ◽  
Rapid Assessment ◽  
Suppressor Gene ◽  
Molecular Heterogeneity ◽  
Liquid Biopsies ◽  
Digital Microfluidic ◽  
Colorectal Cancer Patients

This work presents a digital microfluidic platform called HYPER-Melt (high-density profiling and enumeration by melt) for highly parallelized copy-by-copy DNA molecular profiling. HYPER-Melt provides a facile means of detecting and assessing sequence variations of thousands of individual DNA molecules through digitization in a nanowell microchip array, allowing amplification and interrogation of individual template molecules by detecting HRM fluorescence changes due to sequence-dependent denaturation. As a model application, HYPER-Melt is used here for the detection and assessment of intermolecular heterogeneity of DNA methylation within the promoters of classical tumor suppressor genes. The capabilities of this platform are validated through serial dilutions of mixed epialleles, with demonstrated detection limits as low as 1 methylated variant in 2 million unmethylated templates (0.00005%) of a classic tumor suppressor gene,CDKN2A(p14ARF). The clinical potential of the platform is demonstrated using a digital assay forNDRG4, a tumor suppressor gene that is commonly methylated in colorectal cancer, in liquid biopsies of healthy and colorectal cancer patients. Overall, the platform provides the depth of information, simplicity of use, and single-molecule sensitivity necessary for rapid assessment of intermolecular variation contributing to genetic and epigenetic heterogeneity for challenging applications in embryogenesis, carcinogenesis, and rare biomarker detection.

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