- 著者
- Hengbin QIU Deigui LIN
- 出版者
- 公益社団法人 日本獣医学会
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.15-0557, (Released:2016-02-18)
- 被引用文献数
- 7
The Breast cancer 1, early onset gene (BRCA1) is known to be significantly associated with human familial breast cancer and is identified to play an important role in canine mammary tumors. Here, genetic variations in the coding region and DNA methylation in the 5′ flanking region of BRCA1 in canine mammary tumor samples, 15 each of benign and malignant against 10 normal canine mammary tissue samples, were analyzed using the direct sequencing method. The results indicated two point mutations each in the coding region of canine BRCA1 in one benign mammary tumor sample (4702G>T and 4765G>T) and in one malignant canine mammary tumor sample (3619A>G and 4006G>A). No mutations were detected in the normal canine mammary tissue samples. The 4702G>T mutation was found to terminate further translation. The physical effect of the 4765G>T mutation was found to be the repalacement of the glutamate residue with glutamine. The physical effect of the 3619A>G mutation was found to be the replacement of the threonine residue with alanine, and that of mutation 4006G>A was the replacement of the valine residue with isoleucine in the BRCA1 protein. Bisulfite sequencing detected methylated CpG sites in one canine malignant mammary tumor sample. In conclusion, the present study elucidated the mutational status of the BRCA1 coding region and methylation status of the 5′ flanking region of BRCA1 in canine mammary tumors.
- 著者
- Huanan WANG Xu YANG Yipeng JIN Shimin PEI Di ZHANG Wen MA Jian HUANG Hengbin QIU Xinke ZHANG Qiuyue JIANG Weidong SUN Hong ZHANG Degui LIN
- 出版者
- 公益社団法人 日本獣医学会
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.14-0484, (Released:2015-07-09)
CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease, and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy.
- 著者
- Weidong SUN Xu YANG Hengbin QIU Di ZHANG Huanan WANG Jian HUANG Degui LIN
- 出版者
- 公益社団法人 日本獣医学会
- 雑誌
- Journal of Veterinary Medical Science (ISSN:09167250)
- 巻号頁・発行日
- pp.15-0044, (Released:2015-07-05)
- 被引用文献数
- 1 3
The BRCA1 gene plays an important role in the development of human breast cancer, and recent research indicated that genetic variations of BRCA1 are also related to canine mammary tumors (CMTs). Here, using rapid amplification of cDNA ends (RACE), we cloned the 5′- and 3′-UTRs of BRCA1. By direct sequencing of the flanking sequences of the 5′- and 3′-UTRs of BRCA1, three previously unreported single-nucleotide polymorphisms (SNPs) were identified, two (−1228T>C, −1173C>T) in the putative promoter regions and one non-synonymous SNP (63449G>A) in exon 23. Compared with 16 normal samples, the sequences from 34 CMTs suggested that SNP (−1173C>T) was associated with the development of CMTs (odds ratio (OR)=2.57, 95% confidence interval (CI): 1.07–6.15).