Spontaneous feline mammary carcinoma is a model of HER2 overexpressing poor prognosis human breast cancer

Companion animal spontaneous tumors are suitable models for human cancer, primarily because both animal population and the tumors are genetically heterogeneous. Feline mammary carcinoma (FMC) is a highly aggressive, mainly hormone receptor-negative cancer, which has been proposed as a model for poor...

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Published in:	Cancer research (Chicago, Ill.) Vol. 65; no. 3; pp. 907 - 912
Main Authors:	DE MARIA, Raffaella, OLIVERO, Martina, IUSSICH, Selina, NAKAICHI, Munekazu, MURATA, Tomoaki, BIOLATTI, Bartolomeo, DI RENZO, Maria Flavia
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-02-2005
Subjects:	Animals Antineoplastic agents Biological and medical sciences Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - veterinary Cats Cell Line, Tumor Disease Models, Animal Female Genes, erbB-2 - genetics Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Mammary gland diseases Mammary Glands, Animal - metabolism Medical sciences Pharmacology. Drug treatments Prognosis Receptor, ErbB-2 - biosynthesis Receptor, ErbB-2 - genetics Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - biosynthesis RNA, Messenger - genetics Tumors Human Breast carcinoma Mammary gland diseases Prognosis C-Onc gene Spontaneous erbB2 Gene Gene overexpression Models Breast cancer Malignant tumor Protooncogene
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Abstract	Companion animal spontaneous tumors are suitable models for human cancer, primarily because both animal population and the tumors are genetically heterogeneous. Feline mammary carcinoma (FMC) is a highly aggressive, mainly hormone receptor-negative cancer, which has been proposed as a model for poor prognosis human breast cancer. We have identified and studied the feline orthologue of the HER2 gene, which is both an important prognostic marker and therapeutic target in human cancer. Feline HER2 (f-HER2) gene kinase domain is 92% similar to the human HER2 kinase. F-HER2-specific mRNA was found 3- to 18-fold increased in 3 of 3 FMC cell lines, in 1 of 4 mammary adenomas and 6 of 11 FMC samples using quantitative reverse transcription-PCR. Western blot showed that an anti-human HER2 antibody recognized a protein comigrating with the human p185HER2 in FMC cell lines. The same antibodies strongly stained 13 of 36 FMC archival samples. These data show that feline HER2 overexpression qualifies FMC as homologous to the subset of HER2 overexpressing, poor prognosis human breast carcinomas and as a suitable model to test innovative approaches to therapy of aggressive tumors.
AbstractList	Companion animal spontaneous tumors are suitable models for human cancer, primarily because both animal population and the tumors are genetically heterogeneous. Feline mammary carcinoma (FMC) is a highly aggressive, mainly hormone receptor–negative cancer, which has been proposed as a model for poor prognosis human breast cancer. We have identified and studied the feline orthologue of the HER2 gene, which is both an important prognostic marker and therapeutic target in human cancer. Feline HER2 (f-HER2) gene kinase domain is 92% similar to the human HER2 kinase. F-HER2–specific mRNA was found 3- to 18-fold increased in 3 of 3 FMC cell lines, in 1 of 4 mammary adenomas and 6 of 11 FMC samples using quantitative reverse transcription-PCR. Western blot showed that an anti-human HER2 antibody recognized a protein comigrating with the human p185HER2 in FMC cell lines. The same antibodies strongly stained 13 of 36 FMC archival samples. These data show that feline HER2 overexpression qualifies FMC as homologous to the subset of HER2 overexpressing, poor prognosis human breast carcinomas and as a suitable model to test innovative approaches to therapy of aggressive tumors.
Author	DE MARIA, Raffaella MURATA, Tomoaki BIOLATTI, Bartolomeo OLIVERO, Martina NAKAICHI, Munekazu DI RENZO, Maria Flavia IUSSICH, Selina
Author_xml	– sequence: 1 givenname: Raffaella surname: DE MARIA fullname: DE MARIA, Raffaella organization: Department of Animal Pathology, School of Veterinary Medicine, University of Turin, Grugliasco, Italy – sequence: 2 givenname: Martina surname: OLIVERO fullname: OLIVERO, Martina organization: Laboratory of Cancer Genetics and Comparative Oncology Center of the Institute for Cancer Research and Treatment, University of Turin, Candiolo, Turin, Italy – sequence: 3 givenname: Selina surname: IUSSICH fullname: IUSSICH, Selina organization: Department of Animal Pathology, School of Veterinary Medicine, University of Turin, Grugliasco, Italy – sequence: 4 givenname: Munekazu surname: NAKAICHI fullname: NAKAICHI, Munekazu organization: Department of Veterinary Surgery, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan – sequence: 5 givenname: Tomoaki surname: MURATA fullname: MURATA, Tomoaki organization: Science Research Center, Yamaguchi University, Ube, Yamaguchi, Japan – sequence: 6 givenname: Bartolomeo surname: BIOLATTI fullname: BIOLATTI, Bartolomeo organization: Department of Animal Pathology, School of Veterinary Medicine, University of Turin, Grugliasco, Italy – sequence: 7 givenname: Maria Flavia surname: DI RENZO fullname: DI RENZO, Maria Flavia organization: Laboratory of Cancer Genetics and Comparative Oncology Center of the Institute for Cancer Research and Treatment, University of Turin, Candiolo, Turin, Italy
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SubjectTerms	Animals Antineoplastic agents Biological and medical sciences Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - veterinary Cats Cell Line, Tumor Disease Models, Animal Female Genes, erbB-2 - genetics Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Mammary gland diseases Mammary Glands, Animal - metabolism Medical sciences Pharmacology. Drug treatments Prognosis Receptor, ErbB-2 - biosynthesis Receptor, ErbB-2 - genetics Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - biosynthesis RNA, Messenger - genetics Tumors
Title	Spontaneous feline mammary carcinoma is a model of HER2 overexpressing poor prognosis human breast cancer
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