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Originally published online as doi:10.2353/ajpath.2009.081124 on June 18, 2009

Published online before print June 18, 2009
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(American Journal of Pathology. 2009;175:201-206.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.081124

Expression and Functional Regulation of Myoglobin in Epithelial Cancers

Simona Emilia Flonta*, Sabrina Arena*, Alberto Pisacane{dagger}, Paolo Michieli{ddagger} and Alberto Bardelli*§

From the Laboratory of Molecular Genetics,* the Unit of Pathology,{dagger} and the Division of Molecular Oncology,{ddagger} Institute for Cancer Research and Treatment, University of Turin Medical School, Turin; and the FIRC Institute of Molecular Oncology,§ Milan, Italy

Myoglobin is a multifunctional heme protein that is thought to be expressed exclusively in myocytes. Its importance in both oxygen transport and free radical scavenging has been extensively characterized. We hypothesized that solid tumors could take advantage of proteins such as myoglobin to cope with hypoxic conditions and to control the metabolism of reactive oxygen and nitrogen species. We therefore sought to establish whether myoglobin might be expressed and functionally regulated in epithelial tumors that are known to face hypoxia and oxidative stress during disease progression. We analyzed the expression of myoglobin in human epithelial cancers at both transcriptional and protein levels; moreover, we investigated the expression levels of myoglobin in cancer cell lines subjected to different conditions, including hypoxia, oxidative stress, and mitogenic stimuli. We provide evidence that human epithelial tumors, including breast, lung, ovary, and colon carcinomas, express high levels of myoglobin from the earliest stages of disease development. In human cancer cells, myoglobin is induced by a variety of signals associated with tumor progression, including mitogenic stimuli, oxidative stress, and hypoxia. This study provides evidence that myoglobin, previously thought to be restricted to myocytes, is expressed at high levels by human carcinoma cells. We suggest that myoglobin expression is part of a cellular program aimed at coping with changed metabolic and environmental conditions associated with neoplastic growth.


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