title: Autocrine/paracrine erythropoietin signalling promotes JAK/STAT-dependent proliferation of human cervical cancer cells.
abstract: Erythropoietin (Epo) regulates erythropoiesis by binding to its receptor (EpoR) and promoting cell proliferation, differentiation and inhibition of apoptosis. Epo is widely used to treat cervical cancer-related anaemia. However, there are data suggesting that administration of Epo is associated with an increment in recurrence rate, and decreased disease-free and overall survival. In the present study, we investigated the expression of Epo and EpoR on cervical cancer cell lines. We observed that both EpoR and extracellular Epo are constitutively expressed in cervical cancer cells. Inhibition of either Epo or EpoR expression with siRNA attenuated cell proliferation, whereas addition of exogenous Epo led to a significant increase in cell growth, both in vitro and in vivo. Epo-induced proliferation was associated with the activation of JAK2, JAK3, STAT3 and STAT5 but not JAK1 and STAT1. Our results are consistent with the existence of a functional, endogenous Epo/EpoR system in cervical cancer with the capacity to activate the transduction of signals resulting in an increased proliferation potential.
authors: Instituto de Investigaciones Biomedicas, Departamento de Biologia Molecular y Biotecnologia, UNAM, Mexico City, Mexico.
authors: Tania V
authors: TV
authors: Lopez
authors: Terence R J
authors: TR
authors: Lappin
authors: Perry
authors: P
authors: Maxwell
authors: Zhanzhong
authors: Z
authors: Shi
authors: Rebeca
authors: R
authors: Lopez-Marure
authors: Cecilia
authors: C
authors: Aguilar
authors: Leticia
authors: L
authors: Rocha-Zavaleta
mesh_terms: D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D015153:Blotting, Western; D049109:Cell Proliferation; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D053616:Janus Kinase 3 / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D004921:Erythropoietin; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D053612:Janus Kinases