Ionizing Radiation Induces Cell Cycle G1 Arrest and Tumor Suppressor Gene P16, P21, P27 Expression in Keloid Fibroblasts

2013 ◽  
Vol 87 (2) ◽  
pp. S629 ◽  
Author(s):  
J. Ji ◽  
Y. Tian ◽  
S. Ji ◽  
L. Zhang ◽  
Y. Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Ionizing Radiation ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
G1 Arrest ◽  
Keloid Fibroblasts

The tumor suppressor gene DLEC1 is frequently silenced by DNA methylation in hepatocellular carcinoma and induces G1 arrest in cell cycle

2008 ◽  
Vol 48 (3) ◽  
pp. 433-441 ◽  
Author(s):  
Guo-Hua Qiu ◽  
Manuel Salto-Tellez ◽  
James A. Ross ◽  
Winnie Yeo ◽  
Yan Cui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
G1 Arrest

Neuroradiology Manifestations of Li-Fraumeni Syndrome: Epidemiology, Genetics, Imaging Findings, and Management

Neurographics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 228-235
Author(s):  
S. Naganawa ◽  
T. Donohue ◽  
A. Capizzano ◽  
Y. Ota ◽  
J. Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Soft Tissue Sarcomas ◽  
Suppressor Gene ◽  
Imaging Findings ◽  
Li Fraumeni Syndrome ◽  
Increased Risk ◽  
Li Fraumeni ◽  
Risk Of Cancer

Li-Fraumeni syndrome is a familial cancer predisposition syndrome associated with germline mutation of the tumor suppressor gene 53, which encodes the tumor suppressor p53 protein. Affected patients are predisposed to an increased risk of cancer development, including soft-tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, among other malignancies. The tumor suppressor gene TP53 plays an important, complex role in regulating the cell cycle, collaborating with transcription factors and other proteins. The disruption of appropriate cell cycle regulation by mutated TP53 is considered to be the cause of tumorigenesis in Li-Fraumeni syndrome. Appropriate surveillance, predominantly by using MR imaging, is used for early malignancy screening in an effort to improve the survival rate among individuals who are affected. Patients with Li-Fraumeni syndrome are also at increased risk for neoplasm development after radiation exposure, and, therefore, avoiding unnecessary radiation in both the diagnostic and therapeutic settings is paramount. Here, we review the epidemiology, genetics, imaging findings, and the current standard surveillance protocol for Li-Fraumeni syndrome from the National Comprehensive Cancer Network as well as potential treatment options.Learning Objective: Describe the cause of second primary malignancy among patients with Li-Fraumeni syndrome.

Role of the p16 tumor suppressor gene in cancer.

1998 ◽  
Vol 16 (3) ◽  
pp. 1197-1206 ◽  
Author(s):  
W H Liggett ◽  
D Sidransky
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Human Cancer ◽  
Suppressor Gene ◽  
Premalignant Lesions ◽  
Early Event ◽  
Cyclin Dependent Kinase ◽  
Primary Tumors

Since its discovery as a CDKI (cyclin-dependent kinase inhibitor) in 1993, the tumor suppressor p16 (INK4A/MTS-1/CDKN2A) has gained widespread importance in cancer. The frequent mutations and deletions of p16 in human cancer cell lines first suggested an important role for p16 in carcinogenesis. This genetic evidence for a causal role was significantly strengthened by the observation that p16 was frequently inactivated in familial melanoma kindreds. Since then, a high frequency of p16 gene alterations were observed in many primary tumors. In human neoplasms, p16 is silenced in at least three ways: homozygous deletion, methylation of the promoter, and point mutation. The first two mechanisms comprise the majority of inactivation events in most primary tumors. Additionally, the loss of p16 may be an early event in cancer progression, because deletion of at least one copy is quite high in some premalignant lesions. p16 is a major target in carcinogenesis, rivaled in frequency only by the p53 tumor-suppressor gene. Its mechanism of action as a CDKI has been elegantly elucidated and involves binding to and inactivating the cyclin D-cyclin-dependent kinase 4 (or 6) complex, and thus renders the retinoblastoma protein inactive. This effect blocks the transcription of important cell-cycle regulatory proteins and results in cell-cycle arrest. Although p16 may be involved in cell senescence, the physiologic role of p16 is still unclear. Future work will focus on studies of the upstream events that lead to p16 expression and its mechanism of regulation, and perhaps lead to better therapeutic strategies that can improve the clinical course of many lethal cancers.

Translational significance of a newly identified hepatocellular carcinoma tumor suppressor gene on chromosome 8p.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15097-e15097
Author(s):  
Han Chong Toh ◽  
Francis Enane ◽  
Marissa Teo ◽  
Hideki Makishima ◽  
JoAnna Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Biological Significance ◽  
Suppressor Gene ◽  
Cell Cycle Exit ◽  
Malignant Liver

e15097 Background: After deletion of 17p that removes the tumor suppressor gene (TSG) TP53, deletion of 8p is the next most common chromosome abnormality in hepatocellular carcinoma (HCC). However, 8p TSG are insufficiently defined. Methods: Integrated genomic analysis of HCC and non-malignant liver obtained at therapeutic segmentectomy from the same patients. Results: A minimally deleted region on 8p was identified by SNP array. This incorporated GATA4. Therefore, GATA4 was Sanger sequenced in paired HCC/non-malignant liver: recurrent somatic non-synonymous missense mutations were identified in exon 4 (V267M n=5) or exon 6 (S357T n=6, R362N n=2, T366R n=2). Biallelic abnormalities were deletion and mutation (n=6) or mutation and uniparental disomy (n=4), with mutation or deletion of at least one GATA4 allele in 29/47 (62%) of HCC cases. The other GATA4 exons were mutation free. Although missense mutation is not intrinsically expected to decrease GATA4 expression, GATA4 mRNA was significantly decreased in cases with mutation as well as deletion (p<0.01) compared to non-malignant liver or wild-type GATA4 HCC. GATA4 drives liver differentiation, and the biological significance of GATA4 deficiency was demonstrated by significant enrichment (49%) for liver differentiation genes (p<1.2exp-124, Benjamini corrected) amongst genes with decreased expression in HCC compared to non-malignant liver. From an oncogenesis perspective, the most important of these hepatocyte genes (e.g., HNF4A, CEBPD) antagonize MYC to terminate proliferation: GATA4 introduction (expression vector) into HCC cells containing mutated or deleted GATA4 (HepG2 and PLC respectively) restored HNF4A and CEBPD expression, suppressed MYC protein, upregulated p27/CDKN1B that mediates cell cycle exit by maturation and significantly decreased HCC proliferation without apoptosis. In objectively quantified immunohistochemical analyses (ImageIQ), HCC cases with GATA4 mutation/deletion had significantly increased MYC protein (p<0.05). Conclusions: 8p deletion/GATA4 mutation in HCC suppresses cell cycle exit by maturation, thus complementing 17p deletion that suppresses cell cycle exit by apoptosis.

scholarly journals MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

2010 ◽  
Vol 9 (1) ◽  
pp. 62 ◽  
Author(s):  
Monica Spinola ◽  
Felicia S Falvella ◽  
Francesca Colombo ◽  
James P Sullivan ◽  
David S Shames ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Lung Tumor ◽  
Suppressor Gene

Evaluation of a-Catenin(CTNNA1) As a Tumor Suppressor Gene in Acute Myeloid Leukemis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5240-5240
Author(s):  
Xianwei Zeng ◽  
Ya Liu ◽  
Cui Lv ◽  
Zhenbo Hu
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Suppressor Gene ◽  
Leukemia Cell Line ◽  
G1 Arrest ◽  
Endogenous Expression ◽  
Leukemia Cell Lines

Abstract Abstract 5240 Human a-catenin (CTNNA1) is a 102-kDa cadherin-binding protein that has been recognized as a tumor suppressor gene in solid tumors. Recent studies suggested that a-catenin functional as a tumor suppressor gene in leukemia with 5q deletion as well. In the present study, we speculate that a-catenin may play an important role as a tumor suppressor gene in AML and MDS cases with del(5q), since it is located on chromosome 5, band q31, and within the interval that is consistently deleted in these malignancies. Here, we report the evaluation of a-catenin as a tumor suppressor in myeloid disorders by mutational and functional analysis. Northern blot analysis revealed a very low level of expression of a-catenin mRNA in a panel of leukemia cell lines, whereas it was slightly higher in breast, colon, and prostate cancer lines. Protein truncation analysis in 11 myeloid leukemia cell lines revealed no mutations. By genomic sequencing selected exons in 23 clinical samples of AML/MDS patients with del(5q), we found that 1 of the samples carries a mismatch mutation on exon 5 of the gene. Using pcDNA-catenin expression vector for gene transfection analysis, we found that constitutive expression of a-catenin in the del(5q) leukemia cell line MUTZ-8 inhibited colony formation by 38.7%±6.3%(mea±sd) in the catenin-expressing cells when compared to those with empty vector and caused G1 arrest in the catenin-expressing cells (85.2%±7.3% vs 65.1%±4.6% in control cells) by cell cycle analysis. We conclude that a-catenin causes growth suppression in myeloid leukemia cells, which is consistent with a tumor suppressor gene, and endogenous expression of a-catenin is decreased in most of these cells; However, the finding a-catenin mutation in 1 out of 23 leukemia samples provides limited evidence that it is mutationally inactivated in human leukemias. Disclosures: No relevant conflicts of interest to declare.

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