Tumor cells respond to hypoxia by adapting gene expression through the activation of the transcription factor hypoxia-inducible factor 1 (HIF-1). Hydroxylation of the HIF-1a subunit by prolyl hydroxylase (PHD) oxygen sensors leads to its degradation and inactivation. HIF-1 has been recognized as an accelerating factor in mammary tumor progression and metastasis. In vitro data provide evidence that accumulation of HIF-1 can be modulated by nitric oxide (NO)-releasing substances. Thus, the aim of this study was to examine the influence of the NO donor DETA-NO on tumor growth and metastasis in vivo using an autochthonous mouse model of breast carcinoma. We studied mice that develop mammary tumors over a period of 20 weeks due to expression of the polyoma middle T (PyMT) oncoprotein in mammary epithelial cells. Mice carrying the PyMT transgene were injected every third day intra-peritoneally with DETA-NO or saline at an age of eight weeks over a period of 12 weeks.Our data suggest that treatment with DETA-NO results in an accelerated tumor onset, higher tumor burden and increased pulmonary metastasis. Further studies including mice with a deletion of HIF-1a in mammary epithelial cells will elucidate the role of HIF-1 in NO-mediated tumor progression and metastasis.