scholarly journals Cancer and Tumour Suppressor p53 Encounters at the Juncture of Sex Disparity

2021 ◽  
Vol 12 ◽  
Author(s):  
Sue Haupt ◽  
Ygal Haupt
Keyword(s):  
Tumour Suppressor ◽  
Redox Activity ◽  
Epigenetic Alterations ◽  
Chief Operating Officer ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Sex Disparities ◽  
Males And Females ◽  
Sex Disparity ◽  
Tumour Suppressor P53

There are many differences in cancer manifestation between men and women. New understanding of the origin of these point to fundamental distinctions in the genetic code and its demise. Tumour suppressor protein p53 is the chief operating officer of cancer defence and critically acts to safeguard against sustained DNA damaged. P53 cannot be ignored in cancer sex disparity. In this review we discuss the greater prevalence and associated death rates for non-reproductive cancers in males. The major tumour suppressor protein p53, encoded in the TP53 gene is our chosen context. It is fitting to ask why somatic TP53 mutation incidence is estimated to be disproportionately higher among males in the population for these types of cancers compared with females? We scrutinised the literature for evidence of predisposing genetic and epigenetic alterations that may explain this sex bias. Our second approach was to explore whether redox activity, either externally imposed or inherent to males and females, may define distinct risks that could contribute to the clear cancer sex disparities.

scholarly journals Tumour suppressor protein p53 regulates the stress activated bilirubin oxidase cytochrome P450 2A6

2015 ◽  
Vol 289 (1) ◽  
pp. 30-39 ◽  
Author(s):  
Hao Hu ◽  
Ting Yu ◽  
Satu Arpiainen ◽  
Matti A. Lang ◽  
Jukka Hakkola ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Tumour Suppressor ◽  
Bilirubin Oxidase ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Cytochrome P450 2A6

scholarly journals The Establishment of a Hyperactive Structure Allows the Tumour Suppressor Protein p53 to Function through P-TEFb during Limited CDK9 Kinase Inhibition

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0146648 ◽  
Author(s):  
Thomas K. Albert ◽  
Claudia Antrecht ◽  
Elisabeth Kremmer ◽  
Michael Meisterernst
Keyword(s):  
Tumour Suppressor ◽  
Kinase Inhibition ◽  
Protein P53 ◽  
Tumour Suppressor Protein

Tumour suppressor protein p53 released by nuclease digestion increases at the onset of rat liver regeneration

1999 ◽  
Vol 31 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Francesc Miró ◽  
Jean-Claude Lelong ◽  
Floria Pancetti ◽  
Nerea Roher ◽  
Arlette Duthu ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Rat Liver ◽  
Tumour Suppressor ◽  
Rat Liver Regeneration ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Nuclease Digestion

Redox regulation of tumour suppressor protein p53: identification of the sites of hydrogen peroxide oxidation and glutathionylation

2013 ◽  
Vol 4 (3) ◽  
pp. 1257 ◽  
Author(s):  
Jenna Scotcher ◽  
David J. Clarke ◽  
C. Logan Mackay ◽  
Ted Hupp ◽  
Peter J. Sadler ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Redox Regulation ◽  
Tumour Suppressor ◽  
Peroxide Oxidation ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Hydrogen Peroxide Oxidation

scholarly journals Multifaceted roles of SAMHD1 in cancer

2021 ◽  
Author(s):  
Katie-May McLaughlin ◽  
Jindrich Cinatl ◽  
Mark N Wass ◽  
Martin Michaelis
Keyword(s):  
Potential Role ◽  
Tumour Suppressor ◽  
Paediatric Cancer ◽  
Systematic Analysis ◽  
Tumour Suppressor Protein ◽  
Bona Fide ◽  
Cancer Types ◽  
Males And Females ◽  
Cancer Outcome

SAMHD1 is discussed as a tumour suppressor protein, but its potential role in cancer has only been investigated in very few cancer types. Here, we performed a systematic analysis of the TCGA (adult cancer) and TARGET (paediatric cancer) databases, the results of which did not suggest that SAMHD1 should be regarded as a bona fide tumour suppressor. SAMHD1 mutations that interfere with SAMHD1 function were not associated with poor outcome, which would be expected for a tumour suppressor. High SAMHD1 tumour levels were associated with increased survival in some cancer entities and reduced survival in others. Moreover, the data suggested differences in the role of SAMHD1 between males and females and between different races. Often, there was no significant relationship between SAMHD1 levels and cancer outcome. Taken together, our results indicate that SAMHD1 may exert pro- or anti-tumourigenic effects and that SAMHD1 is involved in the oncogenic process in a minority of cancer cases. These findings seem to be in disaccord with a perception and narrative forming in the field suggesting that SAMHD1 is a tumour suppressor. A systematic literature review confirmed that most of the available scientific articles focus on a potential role of SAMHD1 as a tumour suppressor. The reasons for this remain unclear but may include confirmation bias and publication bias. Our findings emphasise that hypotheses, perceptions, and assumptions need to be continuously challenged by using all available data and evidence.

scholarly journals Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258543
Author(s):  
Francis Opoku ◽  
Kweku Bedu-Addo ◽  
Nicholas Akinwale Titiloye ◽  
Elijah Atta Manu ◽  
Charity Ameh-Mensah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Histological Grade ◽  
Phenotypic Expression ◽  
Tumour Suppressor ◽  
P53 Expression ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Mdm2 Expression

Background Inactivation or mutation of the tumour suppressor gene p53 or its regulator mouse double minute 2 (MDM2) is the commonest event in breast cancer. These altered genes usually express abnormally high levels of their proteins in many carcinomas. The phenotypic expression of p53 and MDM2 in breast cancer cases in our setting is not known. This study investigated the expression of the tumour suppressor protein p53 and its regulator MDM2, using immunohistochemistry in a Ghana breast cancer cohort. Method A 9-year retrospective cross-sectional study on archived tissue blocks–formalin fixed paraffin embedded tissue (FFPE) was carried out. Demographic data were abstracted. Based on complete clinical data and availability of FFPE archived blocks 203 cases were selected for tissue micro array (TMA) construction. The TMA sections were subjected to immunohistochemistry (IHC) (ER, PR, HER2, p53, and MDM2). Expression of p53 and MDM2 were related to grade and molecular subtypes. Results The age ranged from 17 to 92 years (mean = 49.34 ± 13.74). Most of the cases were high grade; grade II (34.9%) and grade III (55.7%). Fifty-four percent of the cases were triple negative. Invasive ductal carcinoma no special type was the commonest histotype (87.1%). Thirty-six percent (36%) of the cases expressed p53. Significant associations were found between p53 overexpression and histological grade (p = 0.034), triple negative (p = 0.0333) and luminal B (p<0.01) tumors. Most cases (93.1%) were negative for MDM2 expression. Significant association was found between MDM2 and HER2 over-expression as well as Ki-67. There was no significant positive correlation between MDM2 and p53 co-expression (p>0.05). Conclusion The elevated level of p53 expression in the aggressive breast cancer phenotypes (high histological grade and triple negative) in our cohort suggest that P53 elevation may be a poor prognostic marker in our setting. High expression of MDM2 in our cohort with high Ki67; also in cases with Her2/neu overexpression known with predictable poor prognosis in the absence of target therapy suggest MDM2 may be associated with aggressive biological behaviour in our breast cancer cases. The non-significant association of p53 and MDM2 expression in the same cases as also documented by previous studies suggest independent genetic pathway in tumourigenesis.

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