Mammary tumor latency is increased in mice lacking the inducible nitric oxide synthase.

Abstract:

:Nitric oxide (NO) and its metabolites are implicated in carcinogenesis and metastasis. Both stimulatory and inhibitory effects of NO have been reported in relation to breast cancer and its role in the development of malignancies and metastasis remains uncertain. We have used the polyomavirus middle T antigen (PyV-mT) targeted to the mouse mammary gland and bred into an inducible NO synthase (iNOS)-deficient C57Bl/6 strain to examine a role for nitric oxide in modulating tumors that develop in the complex environment of the whole animal. The development of hyperplasias was delayed to the extent that the earliest palpable tumors arose 2-4 weeks later in PyV-mT/iNOS(-/-) mice compared with PyV-mT/iNOS(+/+) mice, identifying a role for iNOS in early events in mammary tumor formation. Tumors that did develop in PyV-mT/iNOS(-/-) mice were characteristically well differentiated and had a cribriform pattern. Other tumors were myoepithelial adenocarcinomas with uniform nuclear size. In contrast, mice capable of iNOS activity typically developed solid nodular adenocarcinomas with a high mitotic index and pleomorphic nuclei. No significant effect of iNOS deficiency was found on vascular density in hyperplasias or tumors by examining CD31-positive vessels. The infiltration of lesions by macrophages, cells capable of significant NO production, remained unchanged in PyV-mT/iNOS(-/-) mice. Metastatic potential was retained by PyV-mT-transformed epithelium in the absence of iNOS, indicating that NO production by iNOS is not essential for this process. These results indicate a role for iNOS in tumorigenesis, particularly in the regulation of early events.

journal_name

Int J Cancer

authors

Ellies LG,Fishman M,Hardison J,Kleeman J,Maglione JE,Manner CK,Cardiff RD,MacLeod CL

doi

10.1002/ijc.11178

keywords:

subject

Has Abstract

pub_date

2003-08-10 00:00:00

pages

1-7

issue

1

eissn

0020-7136

issn

1097-0215

journal_volume

106

pub_type

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