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Published on: June 7, 2019
Reduced canine BRCA2 expression levels in mammary gland tumors
Yasunaga Yoshikawa1, Masami Morimatsu2, Kazuhiko Ochiai3
1Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori, 034-8628, Japan. yyoshika@vmas.kitasato-u.ac.jp.
Background:
Mammary tumors are the most common tumor type in intact female dogs. Recently, the breast cancer 2 early onset (BRCA2) gene was proposed to be associated with tumorigenesis in dogs. The expression level of BRCA2 is important for its DNA repair function in mammalian cells, and its expression level is linked to tumorigenesis in mammary tissue. However, the expression of canine BRCA2 in mammary tumors is unclear.
Results:
BRCA2 mRNA levels were compared between seven mammary gland samples and seventeen mammary tumor samples isolated from dogs. The expression level of canine BRCA2 in mammary tumor samples was lower than levels in mammary gland samples. We attempted to identify why the BRCA2 expression level was decreased in mammary tumor samples by promoter sequencing analysis; however, we did not find any mutations in the canine BRCA2 promoter that altered BRCA2 transcription levels. We did detect two types of BRCA2 splice variants in 8 mammary tumor samples. One of the variants induced a frame-shift mutation that could lead to nonsense-mediated mRNA decay, a ubiquitous cellular mechanism that eliminates mRNA containing a premature termination codon.
Conclusions:
Reduced expression of canine BRCA2 mRNA in mammary tumor samples is a possible mechanism to explain mammary tumor development in dogs. One possible reason for reduced BRCA2 mRNA levels in these tumor samples was nonsense-mediated mRNA decay, not mutations in the BRCA2 promoter region. While it remains unclear why canine BRCA2 expression levels are reduced in mammary tumor samples, this study found that the expression level of BRCA2 was associated with canine mammary tumorigenesis.
Insights
Reduced expression of the breast cancer 2 early onset (BRCA2) gene in canine mammary tumors may contribute to their development. Nonsense-mediated mRNA decay, not promoter mutations, appears to be a cause for lower BRCA2 mRNA levels.
Area of Science:
- Veterinary Oncology
- Molecular Biology
- Canine Genetics
Background:
- Mammary tumors are the most frequent cancer in intact female dogs.
- The breast cancer 2 early onset (BRCA2) gene plays a crucial role in DNA repair and is implicated in mammalian tumorigenesis.
- The specific role and expression of BRCA2 in canine mammary tumors remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression levels of BRCA2 mRNA in canine mammary tumors.
- To explore potential mechanisms, such as promoter mutations and splice variants, contributing to altered BRCA2 expression in these tumors.
Main Methods:
- Quantitative comparison of BRCA2 mRNA levels between normal mammary gland and mammary tumor samples from dogs.
- Analysis of the BRCA2 promoter region for mutations.
- Identification and characterization of BRCA2 splice variants in tumor samples.
Main Results:
- Canine BRCA2 mRNA expression was significantly lower in mammary tumor samples compared to normal mammary gland samples.
- No mutations affecting BRCA2 transcription were identified in the promoter region.
- Two types of BRCA2 splice variants were detected, one of which could trigger nonsense-mediated mRNA decay.
Conclusions:
- Reduced BRCA2 mRNA expression is a potential factor in canine mammary tumor development.
- Nonsense-mediated mRNA decay is a likely mechanism for decreased BRCA2 mRNA levels, rather than promoter mutations.
- The association between BRCA2 expression levels and canine mammary tumorigenesis warrants further investigation.
