Amplification of the c-yes Oncogene in Canine Mammary Tumors.

Rungsipipat, Anudep; Tateyama, Susumu; Yamaguchi, Ryoji; Uchida, Katsuhisa; Murakami, Yûichi; Miyoshi, N.; Hayashi, Toshiharu

doi:10.1292/jvms.61.185

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…Either the p16/INK4A and Rb pathway was defective suggesting a defect in cell cycle exit or the p53/p21 pathway was defective suggesting apoptotic signaling may be inoperative [Medema et al, 1995; Bird, 2008]. Coupled to previously identified c‐ erb B‐2 overexpression in all three cell lines and the potential for c‐ yes oncogene activation in such canine tumors, we have proposed a putative model for spontaneous canine mammary cancer [Miyoshi et al, 1991; Ahern et al, 1996; Rungsipipat et al, 1999; Bird, 2008]. Such detailed genetic characterization places these cell lines and canine mammary cancers as highly comparable intermediate models between murine and human breast cancers (Table I).…”

Section: Discussionmentioning

confidence: 66%

Phenotype‐rescue of cyclin‐dependent kinase inhibitor p16/INK4A defects in a spontaneous canine cell model of breast cancer

DeInnocentes

Agarwal

Bird

2009

J of Cellular Biochemistry

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Mammary cancer is among the most frequently observed canine tumors in unspayed female dogs resulting in death due to metastatic disease. These tumors are excellent models of human breast cancer but until recently there was only anecdotal evidence regarding underlying genetic defects. We recently reported expression defects in the cyclin-dependent kinase p21/Cip1 and p53 among three independent canine mammary tumor (CMT) cell lines derived from spontaneous canine mammary cancers. We investigated further defects in the same three cell lines focusing on additional tumor suppressor gene defects in cyclin-dependent kinase inhibitors. p27/KIP1 appeared normally expressed and did not appear to encode inactivating mutations. In contrast, expression of p16/INK4A was defective/absent in two cell lines and normal/slightly induced in the third cell line. To determine if defects were causative in maintaining the transformed phenotype, a p16/INK4A transgene was permanently transfected followed by selection and single cell cloning. CMT/p16 clones were characterized for transgene expression, p16 protein content and phenotype including proliferation rate, cell cycle phase distribution, contact inhibition, substrate dependent cell growth and cell morphology. All cell lines appeared unique yet clear indications of phenotype rescue due to p16/INK4A transgene complementation were observed suggesting that defects in p16 expression were present in all three. In some cases cellular senescence also appeared to be induced. These data provide evidence supporting p16/INK4A mutations as causative defects promoting transformation in canine mammary cancer and further characterizes tumor suppressor gene defects with functional consequences in these cells supporting their application as spontaneous animal models of human disease.

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Section: Discussionmentioning

confidence: 66%

Phenotype‐rescue of cyclin‐dependent kinase inhibitor p16/INK4A defects in a spontaneous canine cell model of breast cancer

DeInnocentes

Agarwal

Bird

2009

J of Cellular Biochemistry

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“…Canine studies have shown increased levels of both the protein and mRNA of c-erbB-2 in malignant but not in normal or benign tissues(Ahern et al 1996;Dutra et al 2004;Rungsipipat et al 1999a). The human oncogenes COX-2 and c-yes-1 have also been documented to be aberrantly expressed in canine mammary cancers(Dore et al 2003;Heller et al 2005;Miyoshi et al 1991;Queiroga et al 2005a;Rungsipipat et al 1999a;Rungsipipat et al 1999b). Four heat shock proteins (Hsp27, Hsp72, Hsp73, and Hsp90) were analyzed using canine mammary tissue from 3 normals and 30 malignant cases(Romanucci et al 2006).…”

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confidence: 99%

MicroRNA expression in canine mammary cancer

et al. 2008

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MicroRNAs (miRNAs) are 18-22-nt noncoding RNAs that are involved in post-transcriptional regulation of genes. Oncomirs, a subclass of miRNAs, include genes whose expression, or lack thereof, are associated with cancers. Until the last decade, the domestic dog was an underused model for the study of various human diseases that have genetic components. The dog exhibits marked genetic and physiologic similarity to the human, thereby making it an excellent model for study and treatment of various hereditary diseases. Furthermore, because the dog presents with distinct, spontaneously occurring mammary tumors, it may serve as a model for genetic analysis and treatments of humans with malignant breast tumors. Because miRNAs have been found to act as both tumor suppressors and oncogenes in several different cancers, expression patterns of ten miRNAs (miR-15a, miR-16, miR-17-5p, miR-21, miR-29b, miR-125b, miR-145, miR-155, miR-181b, let-7f) known to be associated with human breast cancers were compared to malignant canine mammary tumors (n = 6) and normal canine mammary tissue (n = 10). Resulting data revealed miR-29b and miR-21 to have a statistically significant (p < 0.05 by MANOVA analysis) upregulation in cancerous samples. The ten canine miRNAs follow the same pattern of expression as in the human, except for miR-145 which does not show a difference in expression between the normal and cancerous canine samples. In addition, when analyzed according to specific cancer phenotypes, miR-15a and miR-16 show a significant downregulation in canine ductal carcinomas while miRsR-181b, -21, -29b, and let-7f show a significant upregulation in canine tubular papillary carcinomas.

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“…(C) In vitro transcribed 32 P-labeled RNA probes (ARE II-III) were incubated with recombinant purified p38 AUF1 (rAUF1) in the presence or absence of a 1000-fold molar excess of a non-specific (ns) or a specific (s) cold competitor RNA. carcinoma, and a broad range of human cancers, such as colon, breast, head and neck, renal, lung, and stomach cancer [38][39][40].…”

Section: Discussionmentioning

confidence: 99%