Effects of hyperactive Janus kinase 2 signaling in mammary epithelial cells.
Prolactin, the Janus kinase 2 (JAK2) and the signal transducer and activator of transcription 5 (STAT5) are important for mammary gland development and have also been implicated in development and growth of breast tumors. In the present study we have investigated the role for JAK2 in proliferation, differentiation, and apoptosis of the mammary epithelial cell line HC11 by stably overexpressing two hyperactive JAK2 mutants. Cells expressing a JAK2 mutant consisting of only the kinase domain had high amount of nuclear STAT5 protein with low DNA-binding activity, which was rapidly induced to a DNA-binding state by prolactin treatment. Cells expressing JAK2 deleted of the kinase-like domain showed increased sensitivity to prolactin treatment compared to wild type cells. Proliferation was not affected by any of the mutants whereas the ability to undergo apoptosis was decreased implicating a transforming potential of the JAK2 mutants.
Olsen
Hanne
H
Department of Medical Nutrition, Karolinska Institutet, NOVUM, S-141 86, Hudddinge, Sweden.
Hedengran Faulds
Malin A
MA
Saharinen
Pipsa
P
Silvennoinen
Olli
O
Haldosén
Lars Arne
LA
D017209:Apoptosis; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D015342:DNA Probes; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D053614:Janus Kinase 2; D008321:Mammary Glands, Animal / Q000166:cytology / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D053614:Janus Kinase 2