title: Erythropoietin in thyroid cancer.
abstract: Erythropoietin (Epo) and the epo-receptor (EpoR) have been implicated in tumor growth, invasion and metastasis. We previously demonstrated Epo and EpoR expression in a small group of archived papillary thyroid cancers (PTC), but were unable to examine functional integrity using formalin-fixed tissues. In the present study, we examined the in vitro expression, induction and function of Epo and EpoR in papillary (NPA), follicular (WRO) and anaplastic (ARO-81) thyroid cancer cells. We found that all three cell lines expressed Epo and EpoR mRNA and that the hypoxia-mimetic cobalt induced Epo expression in all cell lines. None of the growth factors we examined (thyrotropin, vascular endothelial growth factor, IGF-I, or human Epo) altered Epo or EpoR gene expression. Importantly, however, administration of Epo to NPA but not WRO cells resulted in significant alterations in the expression of several mitogenic genes including cyclooxygenase-2 (COX-2), beta-casein (CSN2), wild type p53-induced gene-1 (WIG1) and cathepsin D (CTSD). Epo treated ARO-81 cells only had an increase in CSN2 expression. We conclude that Epo and EpoR are expressed by thyroid cancers and that stimulation of the Epo/EpoR signal pathway results in changes that could impact on the clinical behavior of thyroid cancers.
authors.affiliation: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Yates
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: K
authors.initials: K
authors.lastname: Oakley
authors.forename: A
authors.initials: A
authors.lastname: Helms
authors.forename: R M
authors.initials: RM
authors.lastname: Tuttle
authors.forename: G L
authors.initials: GL
authors.lastname: Francis
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis; D002364:Caseins / Q000096:biosynthesis; D002402:Cathepsin D / Q000096:biosynthesis; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004921:Erythropoietin / Q000494:pharmacology / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D017467:Receptors, Erythropoietin / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D002364:Caseins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017467:Receptors, Erythropoietin; C411296:TP53I3 protein, human; D016159:Tumor Suppressor Protein p53; C436503:ZMAT3 protein, human; D004921:Erythropoietin; D003035:Cobalt; D051546:Cyclooxygenase 2; D002402:Cathepsin D; C018021:cobaltous chloride