PyV-mT-induced parotid gland hyperplasia as detected by altered lectin reactivity is not modulated by inducible nitric oxide deficiency.
The parotid gland was one of the first organs recognised to be sensitive to the transforming effects of polyomavirus. This study examines parotid gland pathology in mice expressing the polyomavirus middle T (PyV-mT) under the control of the mouse mammary tumour virus long terminal repeat (MMTV-LTR) to (1) demonstrate the utility of this model for studying premalignant disease; (2) identify early lesions by lectin staining and (3) determine effects of the inducible nitric oxide synthase (iNOS) in modulating tumorigenesis. The middle T oncogene is expressed in the parotid glands in addition to the mammary glands and results in the formation of parotid hyperplasias in 100% of transgenic female mice. These hyperplasias have the features of intraepithelial neoplasia including hypertrophic cells with prominent nucleoli and abnormal mitoses. Focal areas of parotid hyperplasia can be identified using peanut agglutinin (PNA), a lectin that recognises the tumour associated T antigen. In contrast to normal parotid gland, areas of hyperplasia do not bind PNA. Mice deficient in iNOS, an enzyme implicated in the promotion of tumorigenesis, were bred into the PyV-mT model. The loss of iNOS did not impact on the number or size of parotid gland hyperplasias, suggesting that NO produced by this enzyme is not a key regulator of PyV-mT-induced parotid gland hyperplasia. The consistent development of parotid hyperplasias in PyV-mT mice and clear identification of these lesions by loss of PNA lectin reactivity provides a useful model for studying early molecular changes in parotid tumorigenesis.
Ellies
L G
LG
Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093-0064, USA. lellies@ucsd.edu <lellies@ucsd.edu>
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D003588:Cytopathogenic Effect, Viral; D005260:Female; D017353:Gene Deletion; D006965:Hyperplasia / Q000473:pathology / Q000821:virology; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009857:Oncogenes; D010306:Parotid Gland / Q000473:pathology* / Q000821:virology; D019887:Peanut Agglutinin; D027601:Polyomavirus Infections / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology* / Q000821:virology
D000952:Antigens, Polyomavirus Transforming; D019887:Peanut Agglutinin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse