title: Jak1 deficiency leads to enhanced Abelson-induced B-cell tumor formation.
abstract: The Janus kinase Jak1 has been implicated in tumor formation by the Abelson oncogene. In this study we show that loss of Jak1 does not affect in vitro transformation by v-abl as defined by the ability to induce cytokine-independent B-cell colony formation or establishment of B-cell lines. However, Jak1-deficient, v-abl-transformed cell lines were more tumorgenic than wild-type cells when transplanted subcutaneously into severe combined immunodeficient (SCID) mice or injected intravenously into nude mice. Jak1 deficiency was associated with a loss in the ability of interferon-gamma (IFN-gamma)to induce growth arrest and/or apoptosis of v-abl-transformed pre-B cells or tumor growth in SCID mice. Moreover, IFN-gamma mRNA could be detected in growing tumors, and tumor cells explanted from SCID mice had lost the ability to respond to IFN-gamma in 9 of 20 cases, whereas the response to interferon-alpha (IFN-alpha) remained intact. Importantly, a similar increase in tumorgenicity was observed when IFN-gamma-deficient cells were injected into SCID mice, identifying the tumor cell itself as the main source of IFN-gamma. These findings demonstrate that Jak1, rather than promoting tumorgenesis as previously proposed, is critical in mediating an intrinsic IFN-gamma-dependent tumor surveillance.
authors.affiliation: Department of Pharmacology, Vienna University, Austria. veronika.sexl@univie.ac.at
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
authors.forename: Boris
authors.initials: B
authors.lastname: Kovacic
authors.forename: Roland
authors.initials: R
authors.lastname: Piekorz
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.forename: Dagmar
authors.initials: D
authors.lastname: Stoiber
authors.forename: Angelika
authors.initials: A
authors.lastname: Hoffmeyer
authors.forename: Rita
authors.initials: R
authors.lastname: Liebminger
authors.forename: Oliver
authors.initials: O
authors.lastname: Kudlacek
authors.forename: Eva
authors.initials: E
authors.lastname: Weisz
authors.forename: Kristen
authors.initials: K
authors.lastname: Rothammer
authors.forename: James N
authors.initials: JN
authors.lastname: Ihle
mesh_terms: D000011:Abelson murine leukemia virus; D000818:Animals; D001402:B-Lymphocytes; D002471:Cell Transformation, Neoplastic; D046508:Culture Techniques; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D053613:Janus Kinase 1; D008099:Liver / Q000196:embryology; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009693:Nucleic Acid Hybridization; D016374:Oncogene Proteins v-abl / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016898:Interferon-alpha; D016374:Oncogene Proteins v-abl; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1