title: Involvement of a JAK/STAT pathway inhibitor: cytokine inducible SH2 containing protein in breast cancer.
abstract: Cytokines and growth factors are responsible for inducing the expression of suppressor of cytokine signaling (SOCS) and cytokine-inducible SH2 containing (CIS) proteins. SOCS and CIS proteins are negative regulators of the JAK/STAT pathway, and exert their physiological effects by suppressing the tyrosine kinase activity of cytokine receptors and inhibiting STAT activation. Growth hormone (GH) is considered as a true cytokine and its local production directly contributes to tumor progression. In an initial study, we have found that CIS expression is increased in human breast cancer in proliferative areas corresponding to high level of GH synthesis. The results of the study presented here confirm the presence of a negative feed back loop in MCF7 cells stably transfected with the hGH gene (MCF-hGH). Real-time PCR analysis showed that gene expression levels of CIS were increased by 80% in MCF-hGH cells as compared to control cell line. Similarly, we have found that the level of CIS gene expression is increased by 50% in primary cultures of human breast cancer, reinforcing the pathophysiological impact of CIS. We previously demonstrated that increasing levels of transfected CIS resulted in strong activation of the mitogen-activated protein (MAP) kinase pathway. Thus, CIS protein has been hypothesized as acting like an activator of the MAPK pathway and an inhibitor of the differentiated cells functions mediated through the JAK/STAT pathway. In the present study, we demonstrate the role of CIS protein in tumor progression in particular its positive effects on cell proliferation and colony formation.
authors.affiliation: Physiologie Integrative Cell. Et Mol. Universite Claude Bernard, Villeurbanne, France.
authors.forename: Sahra
authors.initials: S
authors.lastname: Borgés
authors.forename: Elara
authors.initials: E
authors.lastname: Moudilou
authors.forename: Cécile
authors.initials: C
authors.lastname: Vouyovitch
authors.forename: Jean
authors.initials: J
authors.lastname: Chiesa
authors.forename: Peter
authors.initials: P
authors.lastname: Lobie
authors.forename: Hichem
authors.initials: H
authors.lastname: Mertani
authors.forename: Mireille
authors.initials: M
authors.lastname: Raccurt
mesh_terms: D019898:Autocrine Communication; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D019382:Human Growth Hormone; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins