Effects of melatonin on mammary gland lesions in transgenic mice overexpressing N-ras proto-oncogene
Abstract
The oncostatic effects of melatonin on the mammary gland have been studied in transgenic mice carrying the N-ras proto-oncogene under the control of the MMTV-LTR. Female (4-week-old) virgin mice with positive transgenic pedigrees were injected with melatonin (200 micrograms/mouse/ day, five times a week) or vehicle late in the evening. After 5 months of treatment, animals were sacrificed and the mammary glands were dissected for whole mounts, histology, and immunohistochemical analysis with a mouse monoclonal antibody specific for N-ras protein. Mammary glands of control transgenic mice showed different densities of hyperplastic alveolar nodules (HANs) consisting primarily of dysplastic epithelial cells with nuclear atypia and prominent nucleoli. The epithelial cells of HANs showed a high expression of N-ras while no immunostaining was detected in the unaffected mammary parenchyma. Only one (10%) of the control transgenic mice presented an infiltrating ductal carcinoma with the neoplastic cells overexpressing N-ras protein. The mammary glands of melatonin treated mice had a lower density of HANs, absence of epithelial dysplastic cells, and weak immunostaining of N-ras protein in comparison to the vehicle-treated group. None of ...Continue Reading
References
Melatonin inhibition of MCF-7 human breast-cancer cells growth: influence of cell proliferation rate
Citations
The Pathophysiologic Role of Disrupted Circadian and Neuroendocrine Rhythms in Breast Carcinogenesis
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