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: Veronika Sexl, Boris Kovacic, Roland Piekorz, Richard Moriggl, Dagmar Stoiber, Angelika Hoffmeyer, Rita Liebminger, Oliver Kudlacek, Eva Weisz, Kristen Rothammer, James N Ihle
• Journal: Blood (Blood) Vol. 101 Issue 12 Pg. 4937-43 (Jun 15 2003) ISSN: 0006-4971 [Print] United States
• PMID: 12576323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-alpha
• Oncogene Proteins v-abl
• Interferon-gamma
• Protein-Tyrosine Kinases
• Jak1 protein, mouse
• Janus Kinase 1

Topics

• Abelson murine leukemia virus
• Animals
• B-Lymphocytes
• Cell Transformation, Neoplastic
• Culture Techniques
• Interferon-alpha (pharmacology)
• Interferon-gamma (pharmacology)
• Janus Kinase 1
• Liver (embryology)
• Mice
• Mice, Nude
• Mice, SCID
• Neoplasm Transplantation
• Nucleic Acid Hybridization
• Oncogene Proteins v-abl (genetics)
• Protein-Tyrosine Kinases (deficiency, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction