Current biomarkers of canine mammary tumors

Kaszak, Ilona; Ruszczak, Anna; Kanafa, Szymon; Kacprzak, Kamil; Król, Magdalena; Jurka, P.

doi:10.1186/s13028-018-0417-1

Cited by 95 publications

(105 citation statements)

References 129 publications

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“…Two key mutations were also found in BRC repeat 3, a substitution from Threonine to Proline at codon 1425 and Lysine to Arginine at codon 1435, that would affect the affinity between BRC3 and Rad51 and increase the risk of developing breast cancer [78]. The discovery of BRCA2 underexpression in this study contrasts with other studies who report no difference in BRCA2 expression levels between benign and malignant tumors [69]. Thus, BRCA2 plays an important role in the development of breast cancer, but the exact link between BRCA2 expression level and breast cancer tumorigenesis is still unclear.…”

contrasting

confidence: 83%

Section: Mammary Gland Tumorsmentioning

confidence: 99%

“…Mammary tumors make up more than 50% of the neoplasms in female dogs, making it the second most common neoplasia among dogs in general [69]. Miniature Poodles, Dachshunds, Malteses, Yorkshire Terriers, Cocker Spaniels and German Shepherds are the most predisposed breeds [69]. Because the risk of developing mammary tumors is correlated with exposure to estrogen and progesterone from an early age, the risk of developing it increases if the dog is not spayed or is spayed after the age of two [70].…”

Section: Mammary Gland Tumorsmentioning

confidence: 99%

“…Approximately half of all mammary tumors in dogs are malignant, and tumors most often develop in the fourth and fifth mammary glands [70]. The most common type of malignant mammary tumor is tubular carcinoma (adenocarcinoma), followed by papillary carcinoma [69].…”

Section: Mammary Gland Tumorsmentioning

confidence: 99%

“…p53 7 249 R249W 68 p53 5 148 S148R 68 p53 8 271 E271V 68 p53 5 175 H175A 68 p53 5 163 I163F 68 p53 7 245 G245D 68 p53 7 252 L252F 68 p53 5 180 E180X 68 p53 7 245 G245A 64 p53 5 173 V173L 64 p53 8 285 P285S 64 p53 5 129 L129F 64 p53 7 248 R248Q 64 p53 8 297 P297R 64 p53 6 213 R213X 64 BRCA2 11 669 N669D 64 BRCA2 11 801 K801Q 64 BRCA2 11 908 E908Q 62 BRCA2 11 1425 T1425P 61 BRCA2 11 1435 K1435R 62 The most frequently studied biomarker of mammary tumors is Ki-67, a nuclear, non-histone protein, which can only be detected in the cell nucleus during interphase, and during mitosis. Higher levels of Ki-67 are associated with increased chances for metastasis and poorer prognosis [69,83,84]. Another biomarker is PCNA, an auxiliary protein of DNA polymerase δ, involved in the DNA repair process, cell cycle control, chromatin assembly and in RNA transcription [69,…”

Section: Figurementioning

confidence: 99%

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Molecular Mechanisms of Canine Cancers

Cao¹,

Kouznetsova²,

Tsigelny³

2019

obm genet

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Cancer is the leading cause of death in dogs, and 50 percent of dogs over the age of 10 develop cancer at some point. The most common cancers in dogs include lymphoma, mast cell tumors, osteosarcoma, mammary gland tumors, and melanoma, and many of them share marked similarities with their human counterparts. Although canines are afflicted with many of the same types of cancers as humans, the genetic basis behind these cancers are not as well understood. Thus, the aim of this study is to elucidate some of the molecular mechanisms behind canine cancers. Canine lymphoma mutation patterns generally vary with the type of lymphoma afflicted-B-cell lymphomas have mutations in the alternative NF-kB pathway including MAP3K14, whereas in T-cell lymphomas the mTOR pathway in boxers and cellular metabolism genes in golden retrievers are affected. Mast cell tumors are largely traced to internal tandem duplications and deletions in the juxtamembrane domain of the proto-oncogene c-KIT. In osteosarcoma, mutations in RB1 and TP53 (especially G: C->A:T transitions in exons 4 and 5), as well as CDK4 inhibitors CDKN2A/B are common. Mammary gland tumors are associated with BRCA2 underexpression due to reading frame shift and mutations in BRC repeat 3. Lastly, deletion or underexpression of p16 and PTEN and altered expression of cell-cell adhesion molecules are common factors in the development of melanoma. The genes identified were then studied to identify more key amino acid mutations that changed protein products and promoted tumorigenesis. Genes that altered expression levels of proteins were analyzed separately. Both sets of candidate genes were then analyzed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) in order to elucidate the molecular pathways involved in canine cancers and identify more genes possibly involved in tumorigenesis. The proposition of this review is that treatments for both canine and human cancers would be enhanced by comparative genomic studies.

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contrasting

confidence: 83%

Section: Mammary Gland Tumorsmentioning

confidence: 99%

Section: Mammary Gland Tumorsmentioning

confidence: 99%

Section: Mammary Gland Tumorsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Molecular Mechanisms of Canine Cancers

Cao¹,

Kouznetsova²,

Tsigelny³

2019

obm genet

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Genetic analysis of PALB2 gene WD40 domain in canine mammary tumour patients

Çıldır,

Özmen,

Kul

et al. 2024

Veterinary Medicine & Sci

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BackgroundDNA repair mechanisms are essential for tumorigenesis and disruption of HR mechanism is an important predisposing factor of human breast cancers (BC). PALB2 is an important part of the HR. There are similarities between canine mammary tumours (CMT) and BCs. As its human counterpart, PALB2 mutations could be a predisposing factor of CMT.ObjectivesIn this study, we aimed to investigate the impacts of PALB2 variants on tumorigenesis and canine mammary tumor (CMT) malignancy.MethodsWe performed Sanger sequencing to detect germline mutations in the WD40 domain of the canine PALB2 gene in CMT patients. We conducted in silico analysis to investigate the variants, and compared the germline PALB2 mutations in humans that cause breast cancer (BC) with the variants detected in dogs with CMT.ResultsWe identified an intronic (c.3096+8C>G) variant, two exonic (p.A1050V and p.R1354R) variants, and a 3′ UTR variant (c.4071T>C). Of these, p.R1354R and c.4071T>C novel variants were identified for the first time in this study. We found that the p.A1050V mutation had a significant effect. However, we could not determine sufficient similarity due to the differences in nucleotide/amino acid sequences between two species. Nonetheless, possible variants of human sequences in the exact location as their dog counterparts are associated with several cancer types, implying that the variants could be crucial for tumorigenesis in dogs. Our results did not show any effect of the variants on tumor malignancy.ConclusionsThe current project is the first study investigating the relationship between the PALB2 gene WD40 domain and CMTs. Our findings will contribute to a better understanding of the pathogenic mechanism of the PALB2 gene in CMTs. In humans, variant positions in canines have been linked to cancer‐related phenotypes such as familial BC, endometrial tumor, and hereditary cancer predisposition syndrome. The results of bioinformatics analyses should be investigated through functional tests or case‐control studies.

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Anti‐cancer potentials of Gynura procumbens leaves extract against two canine mammary cancer cell lines

Jermnak

Supsavhad

Kunakornsawat

et al. 2021

Veterinary Medicine & Sci

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Background The anti‐cancer effects of Gynura procumbens leaves extract (GPE) have been reported in various human cancers. However, the anti‐cancer effects and molecular mechanisms of this extract on canine mammary cancer (CMC) have not yet been elucidated. Objectives The main goal of this study was to investigate the anti‐cancer properties of GPE against two CMC cell lines (CHMp‐13a and CHMp‐5b). Methods The GP leaves were extracted with 80% ethanol. Anti‐cancer potentials of GPE on CHMp‐13a and CHMp‐5b cancer cell lines using dimethyl‐2‐thiazolyl‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT), wound healing, transwell migration, and caspase 3/7 activity assays were evaluated. The mRNA expression levels of two oncogenes: epidermal growth factor receptor (EGFR) and twist family bHLH transcription factor 1 (TWIST) and one tumour suppressor gene: phosphatase and tensin homolog (PTEN) in these cell lines were determined by quantitative real‐time PCR (qRT‐PCR). In addition, The EGFR and PTEN protein levels as well as protein kinase B (AKT) and extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation levels expression were also evaluated by western blot analysis. Results The results showed that GPE caused a significant concentration‐ and time‐dependent reduction in cell proliferation of both CHMp‐13a and CHMp‐5b cells, detected by MTT assays. This extract also significantly suppressed cancer cell migration in both cell lines, tested by wound healing and transwell migration assays. Additionally, the increase in caspase 3/7 activity observed in both CMC cell treated with GPE suggests that GPE induced caspase 3/7 dependent apoptosis. Moreover, GPE significantly decreased EGFR mRNA and protein expression levels compared to control in both cell lines in a dose‐dependent manner. Conclusion These findings emphasized that GPE has an in vitro anti‐cancer activity against CMC by inhibiting EGFR signalling pathway. Thus, GPE may serve as an alternative therapy in CMC with high EGFR expression.

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Current biomarkers of canine mammary tumors

Cited by 95 publications

References 129 publications

Molecular Mechanisms of Canine Cancers

Molecular Mechanisms of Canine Cancers

Genetic analysis of PALB2 gene WD40 domain in canine mammary tumour patients

Anti‐cancer potentials of Gynura procumbens leaves extract against two canine mammary cancer cell lines

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