Manipulating the p53 Gene in the Mouse: Organismal Functions of a Prototype Tumor Suppressor

Mutations of tumor suppressor genes remove mechanisms that normally arrest proliferation of transformed cells, resulting in tumor formation. The p53 gene product functions as a tumor suppressor that induces p21/Waf-1, the 21-kDa product of the waf-1/cip-1/mda-6 gene. p21/Waf-1 is a pan-cyclin-dependent kinase inhibitor that arrests cell cycle progression under a variety of circumstances. We examined tissues from a dog with multiple primary pigmented proliferative lesions (benign, multicentric melanoma consisting of three distinct dermal lesions and a matrical cyst) for p21/Waf-1 and p53 expression by immunohistochemistry and immunoblotting. p21/Waf-1 and p-53 proteins were undetectable in the tumor cells and in the cyst but were present in adjacent normal tissues. Abundant cyclin-dependent kinase 4 (Cdk4), a protein related functionally to p21/Waf-1, also was present in the cyst. A somatic mutation of the waf-1 gene or of the p53 gene may have resulted in the loss of p21/Waf-1 expression in a common precursor of pigment-producing cells from the affected dog. Furthermore, this functional loss of p21/Waf-1 may play an important role in the genesis of canine benign melanoma.

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Chemical selectivity of nucleobase adduction relative to in vivo mutation sites on exon 7 fragment of p53 tumor suppressor gene

Chemical Science ◽

10.1039/c5sc01403d ◽

2015 ◽

Vol 6 (10) ◽

pp. 5554-5563 ◽

Cited By ~ 5

Author(s):

Spundana Malla ◽

Karteek Kadimisetty ◽

You-Jun Fu ◽

Dharamainder Choudhary ◽

Ingela Jansson ◽

...

Keyword(s):

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

P53 Gene ◽

Suppressor Gene ◽

P53 Tumor Suppressor ◽

P53 Tumor Suppressor Gene ◽

Chemical Selectivity

A 32-bp fragment of P53 gene reacted with benzo[a]pyrene metabolite BPDE was analyzed by LC-MS/MS. Chemically reactive sites were similar to frequently mutated codons in tumors.

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Manipulating the p53 Gene in the Mouse: Organismal Functions of a Prototype Tumor Suppressor

25 Years of p53 Research ◽

10.1007/1-4020-2922-5_8 ◽

2005 ◽

pp. 183-207

Author(s):

Lawrence A. Donehower ◽

Dora Bocangel ◽

Melissa Dumble ◽

Guillermina Lozano

Keyword(s):

Tumor Suppressor ◽

P53 Gene

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Tumor suppressor p53 gene codon 72 polymorphism and imatinib cytogenetic response in chronic myeloid leukemia

Menoufia Medical Journal ◽

10.4103/mmj.mmj_88_16 ◽

2019 ◽

Vol 32 (4) ◽

pp. 1485

Author(s):

YasminA. H Sadek Younis ◽

KhaledAbd Almoamen Khalifa ◽

EnasS Essa ◽

WafaaM Shehata Radwan ◽

EnasA Elkholy

Keyword(s):

Chronic Myeloid Leukemia ◽

Tumor Suppressor ◽

Myeloid Leukemia ◽

P53 Gene ◽

Cytogenetic Response ◽

Tumor Suppressor P53 ◽

Codon 72 ◽

Codon 72 Polymorphism

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Nucleic acid probe based on DNA-templated silver nanoclusters for turn-on fluorescence detection of tumor suppressor gene p53

RSC Advances ◽

10.1039/c8ra04716b ◽

2018 ◽

Vol 8 (45) ◽

pp. 25611-25616 ◽

Cited By ~ 3

Author(s):

Dan Han ◽

Chunying Wei

Keyword(s):

Nucleic Acid ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Fluorescence Detection ◽

P53 Gene ◽

Suppressor Gene ◽

Silver Nanoclusters ◽

Turn On ◽

Ag Ncs ◽

Tumor Suppressor Gene P53

“Turn-on” fluorescence detection for p53 gene based on target-triggered opening of hairpin DNA probe and synthesis of DNA-Ag NCs.

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Immunohistochemical Detection of Tumor Suppressor Gene p53 Protein in Feline Injection Site-associated Sarcomas

Veterinary Pathology ◽

10.1354/vp.38-2-236 ◽

2001 ◽

Vol 38 (2) ◽

pp. 236-238 ◽

Cited By ~ 26

Author(s):

P. R. Nambiar ◽

M. L. Jackson ◽

J. A. Ellis ◽

B. J. Chelack ◽

B. A. Kidney ◽

...

Keyword(s):

Tumor Suppressor ◽

Tumor Cell ◽

Injection Site ◽

Tumor Suppressor Gene ◽

P53 Protein ◽

P53 Gene ◽

Suppressor Gene ◽

Immunohistochemical Detection ◽

Cell Nuclei ◽

P53 Tumor Suppressor Gene

Sarcomas associated with injection sites are a rare but important problem in cats. Immunohistochemical detection of p53 protein may correlate to mutation of the p53 tumor suppressor gene, a gene known to be important in oncogenesis. The expression of nuclear p53 protein in 40 feline injection site-assocated sarcomas was examined by immunohistochemical staining. In 42.5% (17/40), tumor cell nuclei were stained darkly; in 20% (8/40), tumor cell nuclei were stained palely; and in 37.5% (15/40), tumor cell nuclei were unstained. Immunohistochemical detection of p53 protein in a proportion of injection site-associated sarcomas suggests that mutation of the p53 gene may play a role in the pathogenesis of these tumors.

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Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML and loss of one p53 gene: Report of two cases and literature review

Vojnosanitetski pregled ◽

10.2298/vsp170824174d ◽

2019 ◽

Vol 76 (9) ◽

pp. 960-967

Author(s):

Vesna Djordjevic ◽

Marija Dencic-Fekete ◽

Jelica Jovanovic ◽

Marijana Virijevic ◽

Nada Kraguljac-Kurtovic ◽

...

Keyword(s):

Tumor Suppressor ◽

Acute Promyelocytic Leukemia ◽

P53 Gene ◽

Promyelocytic Leukemia ◽

Chromosome 17 ◽

Gene Copy ◽

Fish Analysis ◽

Derivative Chromosome ◽

Tumor Suppressor P53 ◽

Poor Prognostic Factor

Introduction. The isochromosome of the long arm of derivative chromosome 17, that originates from the translocation t(15;17) [ider(17)(q10)t(15;17), or ider(17q)] in acute promyelocytic leukemia (APL), is a rare chromosome aberration associated with a poor prognosis. Case report. We report the clinical and laboratory data associated with ider(17q) for two APL patients. Cytogenetic analysis of bone marrow cells in both cases showed a mosaic karyotype with the ider(17q); reverse transcription polymerase chain reaction (RT-PCR) was positive for the long (L) isoform of the retionic acid receptor alpha (PML-RARA) fusion transcript in each patient. Fluorescence in situ hybridization (FISH) analysis with the DNA probes for the PML gene on 15q24.1, and the RARA gene on 17q21.2, confirmed the extra copy of the RARA-PML fusion gene or ider(17q). Additionally, the FISH analysis with a DNA probe for the p53 gene on 17p13.1 confirmed loss of one copy of the universal tumor suppressor p53 in both patients. Conclusion. Both reported APL patients with ider(17q) had predominance of the clone with ider(17q) compared to those with t(15;17) and/or the normal karyotype, indicating that duplication of der(17) may provide a growth advantage allowing the relevant clone to become dominant. Moreover, as an important oncogenic event and poor prognostic factor in leukemia, loss of one gene copy of the tumor suppressor p53, may also contribute to this growth advantage. Although the clinical and prognostic significance for the patients with an ider(17q) remains unclear, cytogenetic and molecular-genetic analysis should be combined to reveal more details about this complex and rare chromosomal abnormality.

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Pengaruh P53 Dan YY1 Terhadap Terjadinya Kanker Serviks

Medicinus ◽

10.19166/med.v5i1.1177 ◽

2018 ◽

Vol 5 (1) ◽

Author(s):

Jacobus Jeno Wibisono

Keyword(s):

Cervical Cancer ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Gene Activation ◽

P53 Gene ◽

Suppressor Gene ◽

E6 Oncoprotein ◽

P53 Activation ◽

Ubiquitination Pathway ◽

E6 And E7

Cervical cancer is one of the most prevalent cancer in the world and caused by Human Papilloma Virus (HPV). The pathogenesis of cancer as whole (50%) is caused by gene mutation. HPV stimulates carcinogenesis on cervix epitel cells by HPV-Encoded viral oncoproteins, E6 and E7, which will inhibit tumor suppressor gene activation, such as p53 gene. HPV-encoded E6 oncoprotein is able to directly attached on p53 causing degeneration via E6-AP-mediated ubiquitination pathway. Moreover, overexpression on YY1 gene has significant role on the progression of HPV on cervical cancer. YY1 inhibits p53 activation dan inhibits apoptosis on cells infected by HPV. Overexpression of YY1 induces reduction of endogenous p53, which will inhibit p53 function as tumor suppressor gene.Keywords: cervical cancer, HPV, P53, YY1

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