Defect of the mitochondrial DNA hypervariable region as a risk factor for canine mammary tumour

2016 ◽  
Vol 15 (3) ◽  
pp. 820-828 ◽  
Author(s):  
M. Surdyka ◽  
B. Slaska
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Michela Levi ◽  
Roberta Salaroli ◽  
Federico Parenti ◽  
Raffaella De Maria ◽  
Augusta Zannoni ◽  
...  

Abstract Background Doxorubicin (DOX) is widely used in both human and veterinary oncology although the onset of multidrug resistance (MDR) in neoplastic cells often leads to chemotherapy failure. Better understanding of the cellular mechanisms that circumvent chemotherapy efficacy is paramount. The aim of this study was to investigate the response of two canine mammary tumour cell lines, CIPp from a primary tumour and CIPm, from its lymph node metastasis, to exposure to EC50(20h) DOX at 12, 24 and 48 h of treatment. We assessed the uptake and subcellular distribution of DOX, the expression and function of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), two important MDR mediators. To better understand this phenomenon the effects of DOX on the cell cycle and Ki67 cell proliferation index and the expression of p53 and telomerase reverse transcriptase (TERT) were also evaluated by immunocytochemistry (ICC). Results Both cell lines were able to uptake DOX within the nucleus at 3 h treatment while at 48 h DOX was absent from the intracellular compartment (assessed by fluorescence microscope) in all the surviving cells. CIPm, originated from the metastatic tumour, were more efficient in extruding P-gp substrates. By ICC and qRT-PCR an overall increase in both P-gp and BCRP were observed at 48 h of EC50(20h) DOX treatment in both cell lines and were associated with a striking increase in the percentage of p53 and TERT expressing cells by ICC. The cell proliferation fraction was decreased at 48 h in both cell lines and cell cycle analysis showed a DOX-induced arrest in the S phase for CIPp, while CIPm had an increase in cellular death without arrest. Both cells lines were therefore composed by a fraction of cells sensible to DOX that underwent apoptosis/necrosis. Conclusions DOX administration results in interlinked modifications in the cellular population including a substantial effect on the cell cycle, in particular arrest in the S phase for CIPp and the selection of a subpopulation of neoplastic cells bearing MDR phenotype characterized by P-gp and BCRP expression, TERT activation, p53 accumulation and decrease in the proliferating fraction. Important information is given for understanding the dynamic and mechanisms of the onset of drug resistance in a neoplastic cell population.


2016 ◽  
Vol 41 ◽  
pp. 10-14 ◽  
Author(s):  
Punlop Thongngam ◽  
Worraanong Leewattanapasuk ◽  
Tanin Bhoopat ◽  
Padchanee Sangthong

Genomics ◽  
2020 ◽  
Vol 112 (5) ◽  
pp. 3560-3564 ◽  
Author(s):  
Bassim Muften Ohied ◽  
Adnan Issa Al-Badran

2006 ◽  
Vol 84 (10) ◽  
pp. 1431-1439 ◽  
Author(s):  
Xiao-Ming Wang ◽  
Li-Rong Cao ◽  
Zhen-Sheng Liu ◽  
Sheng-Guo Fang

Mitochondrial DNA (mtDNA) control region (5′ hypervariable region, 554 bp) sequences from 71 samples of blue sheep ( Pseudois nayaur Hodgson, 1833) collected from six study localities throughout Helan Mountain Nature Reserve in Ningxia province of China were investigated to analyse distribution patterns of genetic variability, elucidate matrilineal structure, and investigate population history. Haplotype diversity (h) among the 71 samples was estimated to be 0.792 ± 0.037, and nucleotide diversity (Π) was relatively low (0.00392 ± 0.00046). A χ2 contingency analysis of all mtDNA haplotype frequencies revealed that these haplotypes were distributed in a nonrandom fashion among study localities (χ2 = 86.205, P = 0.092). Additional evidence of matrilineal structure was provided by the finding that a significant amount (9.02%; P < 0.01) of mtDNA variation was partitioned among different localities in the study area. We conclude that blue sheep of Helan Mountain Nature Reserve are structured spatially along matrilines. Pairwise computations of Φst and an AMOVA indicated that some sampling localities are differentiated relative to a random collection of genotypes and reflected differences in the spatial distribution of genetic variation. Isolation-by-distance (IBD) models (Mantel tests) revealed no obvious association between genetic differentiation and geographical distance. These results could be a basis for the development of suitable management strategies for conservation purposes. This work represents the first analysis of blue sheep mitochondrial control region DNA to be performed from a population genetics perspective.


Author(s):  
Moses Okpeku ◽  
Sunday O. Peters ◽  
Ikhide G. Imumorin ◽  
Kyle C. Caires ◽  
Varun K. Sharma ◽  
...  

2004 ◽  
Vol 10 (5) ◽  
pp. 532-535 ◽  
Author(s):  
D Otaegui ◽  
A Sáenz ◽  
M Martínez-Zabaleta ◽  
P Villoslada ◽  
I Fernández-Manchola ◽  
...  

Previous studies have suggested that mitochondrial metabolism and/or mitochondrial DNA (mtDNA) could be, in conjunction with other genetic or environmental factors, a risk factor for the development of multiple sclerosis (MS). One of these studies establishes that mitochondrial haplogroup JT is a risk factor for developing the disease, in particular the visual manifestations [optic neuritis (ON)]. Nevertheless, as distribution of these haplogroups varies between populations, the observed association may be due to a slanted sample with no physiopathological value. This hypothesis was checked with MS patients, originals from Basque country (this population has peculiar genetic characteristics) and from other Spanish regions. We concluded that such an association does not exist. By contrast, a decrease could be seen in the frequency of the JT haplogroup in the ON group and in the MS-Basque group. That trend could be a protective effect, which needs to be verified in further investigations.


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