Histopathology of salivary and mammary gland tumors in transgenic mice expressing a human Ha-ras oncogene

Mutated ras genes are powerful transforming agents in vitro and are found in a wide variety of human tumors in vivo. We characterized the histopathology and p21 protein expression associated with tumorigenesis in line 69 transgenic mice carrying an activated, human c-Ha-ras gene on the Y-chromosome...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1991-07, Vol.51 (14), p.3762-3767
Main Authors: NIELSEN, L. L, DISCAFANI, C. M, GURNANI, M, TYLER, R. D
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
carcinoma
Chromosome Mapping
Genes, ras
Male
mammary gland
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - pathology
Medical sciences
Mice
Mice, Transgenic
Neoplasm Metastasis
Otorhinolaryngology. Stomatology
protein p21
Proto-Oncogene Proteins p21(ras) - analysis
salivary gland
Salivary Gland Neoplasms - genetics
Salivary Gland Neoplasms - pathology
Tumors
Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
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Summary:Mutated ras genes are powerful transforming agents in vitro and are found in a wide variety of human tumors in vivo. We characterized the histopathology and p21 protein expression associated with tumorigenesis in line 69 transgenic mice carrying an activated, human c-Ha-ras gene on the Y-chromosome (A. C. Andres, C. A. Schonenberger, B. Groner, L. Hennighausen, M. LeMeur, and P. Gerlinger, Proc. Natl. Acad. Sci. USA, 84: 1299-1303, 1987). Male mice developed salivary and/or mammary gland tumors. The salivary tumors were adenosquamous carcinomas arising from serous areas of the submandibular gland. They characteristically exhibited densely packed cords and sheets of moderately anaplastic cells. Tumorigenic tissue had a high mitotic index, and all tumor-bearing animals had an ongoing inflammatory response as evidenced by extensive immune cell infiltration of affected tissue. Half of the mammary gland tumors were adenosquamous carcinomas with multiple foci of squamous metaplasia, while the rest were adenocarcinomas containing glandular tissue. Most tumors had a high mitotic index, and abnormal mitotic figures were common. All tumors produced p21 ras, as confirmed by immunohistochemistry and Western blots. Both tumor types expressed elevated levels of p21 protein. Microscopic lung metastases were present in 5 of 35 animals (14%). Our results suggest that this transgenic mouse will provide a useful model for testing therapies directed against ras-associated tumorigenesis.
ISSN:0008-5472
1538-7445