著者

Aki FUJIWARA-IGARASHI Yuko GOTO-KOSHINO Hiroyuki MOCHIZUKI Shingo MAEDA Yasuhito FUJINO Koichi OHNO Hajime TSUJIMOTO

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

vol.75, no.6, pp.733-742, 2013 (Released:2013-07-01)

参考文献数

45

被引用文献数

6 11

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The p16, p15 and p14 genes are widely known as tumor suppressor genes in human medicine. Although a large number of genetic and epigenetic aberrations in these genes have been reported in human malignancies, canine malignancies have not been well analyzed on the aberrations of these genes. In this study, the full-length complementary DNA (cDNA) of the canine p16 gene was cloned using the 5’ and 3’ rapid amplification of cDNA ends methods. Based on the sequence data, primers specific for p16, p15 and p14 were designed. Using these primers, the expression of p16, p15 and p14 mRNAs could be individually evaluated by reverse transcriptase polymerase chain reaction. Genomic aberrations were also examined using genomic polymerase chain reaction. Two of the 6 canine lymphoid tumor cell lines did not express detectable levels of p16, p15 and p14 mRNAs, and wide-ranging deletions in the p15-p14-p16 genomic locus were suspected. Wide-ranging deletions were also speculated in 2 of 14 dogs with T-cell lymphoid tumors. On the other hand, similar failure of amplification suggesting wide-ranging deletions were not observed in any of the 14 dogs with B-cell lymphoma. Deletion of the p15-p14-p16 genomic locus could be one of the molecular aberrations in canine lymphoid tumor cells.

著者

Ko KOJIMA Yasuhito FUJINO Yuko GOTO-KOSHINO Koichi OHNO Hajime TSUJIMOTO

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

vol.75, no.6, pp.727-731, 2013 (Released:2013-07-01)

参考文献数

21

被引用文献数

4 8

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Lymphoid malignancies, such as leukemia, and many types of lymphoma are common and severe disorders in dogs. Since shortening remission duration caused by resistance to chemotherapy often becomes clinically critical problems, development of novel and effective therapy should be required. The present study investigated the status of NF-κB and effect of its inhibitor, bortezomib, in six canine neoplastic lymphoid cell lines. NF-κB p65 and p50 were detected in the nuclear fraction of GL-1, CLBL-1 and CL-1, suggesting that NF-κB was constitutively activated in the cells. NF-κB p65 was detected in the cytoplasmic fraction of UL-1 and Ema. After incubation with bortezomib, NF-κB p50 and p65 became undetectable in the nuclear fraction of GL-1, CLBL-1 and CL-1, and CLBL-1, respectively, and p65 was clearly degraded in the cytoplasmic fraction of CLBL-1 and CL-1. Bortezomib inhibited the proliferation of all cell lines except Nody-1 in a concentration-dependent manner. The results indicated that constitutive activation of NF-κB could contribute to the proliferation of canine neoplastic lymphoid cells, and bortezomib would have suppressive effects on the NF-κB activation and the proliferation of neoplastic lymphoid cells in dogs.