Rapamycin-independent IGF2 expression in Tsc2-null mouse embryo fibroblasts and human lymphangioleiomyomatosis cells

PloS One
Blanca E HimesVera P Krymskaya

Abstract

Lymphangioleiomyomatosis (LAM) is a rare, almost exclusively female lung disease linked to inactivating mutations in tuberous sclerosis complex 2 (TSC2), a tumor suppressor gene that controls cell metabolic state and growth via regulation of the mechanistic target of rapamycin (mTORC1) signaling. mTORC1 is frequently activated in human cancers and, although the mTORC1 inhibitor rapamycin has a cytostatic effect, it is, in general, unable to elicit a robust curative effect or tumor regression. Using RNA-Seq, we identified (1) Insulin-like Growth Factor (IGF2) as one of the genes with the highest fold-change difference between human TSC2-null and TSC2-expressing angiomyolipoma cells from a patient with LAM, and (2) the mouse IGF2 homolog Igf2, as a top-ranking gene according to fold change between Tsc2-/- and Tsc2+/+ mouse embryo fibroblasts (MEFs). We extended transcript-level findings to protein level, observing increased Igf2 protein expression and Igf2 secretion by Tsc2-/- MEFs. Increased Igf2 expression was not due to epigenetic imprinting, but was partially mediated through the Stat3 pathway and was completely insensitive to rapamycin treatment. An siRNA-mediated decrease of Igf2 resulted in decreased Stat3 phosphorylation,...Continue Reading

References

Dec 1, 1988·The New England Journal of Medicine·W H DaughadayP Rotwein
Mar 1, 1997·Cytokine & Growth Factor Reviews·D R Clemmons
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·T CarsilloE P Henske
Aug 29, 2001·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·J C ValenciaV J Ferrans
Aug 19, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jane YuElizabeth Petri Henske
Apr 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Khandaker SiddiqueeJames Turkson
Jan 11, 2008·The New England Journal of Medicine·John J BisslerDavid N Franz
Mar 1, 2008·Cytokine & Growth Factor Reviews·Wendy Chao, Patricia A D'Amore
Oct 7, 2008·The Journal of Biological Chemistry·Kepeng WangZhenguo Wu
Nov 26, 2008·Nature Reviews. Cancer·Michael Pollak
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Apr 23, 2009·Science Signaling·David A Guertin, David M Sabatini
May 2, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Sonja E SteigenTorsten O Nielsen
Oct 3, 2009·Trends in Biochemical Sciences·James BrownBriony E Forbes
Jan 2, 2010·The European Respiratory Journal·S R JohnsonUNKNOWN Review Panel of the ERS LAM Task Force
Mar 6, 2010·The American Journal of Pathology·Kuniaki SeyamaNicholas E Vlahakis
Mar 18, 2011·The New England Journal of Medicine·Francis X McCormackUNKNOWN MILES Trial Group
Apr 13, 2011·Molecular and Cellular Biology·Elena A GoncharovaVera P Krymskaya
Jun 8, 2012·EMBO Molecular Medicine·Victoria L HaleyA Bassim Hassan
Jul 26, 2012·EMBO Molecular Medicine·Frederic ClermontJean-Christophe Marine
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Nov 2, 2012·The Journal of Clinical Investigation·Elizabeth P Henske, Francis X McCormack
Oct 2, 2013·Endocrine-related Cancer·Callum Livingstone
Jul 16, 2014·The International Journal of Developmental Biology·Jennifer M KalishMarisa S Bartolomei
Oct 25, 2014·Nature Reviews. Cancer·Hua YuRichard Jove
Dec 17, 2014·American Journal of Respiratory and Critical Care Medicine·Francis X McCormack
Mar 10, 2015·Nature Cell Biology·Jung-Soon MoKun-Liang Guan
Apr 5, 2016·Nature Biotechnology·Nicolas L BrayLior Pachter
Sep 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Stella K HurMarisa S Bartolomei
Dec 23, 2016·EBioMedicine·Vilma BarrocaSylvie-Nathalie Hardouin
Jan 19, 2017·Annual Review of Medicine·Vera P Krymskaya, Francis X McCormack
Mar 12, 2017·Cell·Robert A Saxton, David M Sabatini
Sep 7, 2017·The New England Journal of Medicine·Brendan D Manning

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Datasets Mentioned

BETA
GSE84476
GSE84477

Methods Mentioned

BETA
RNA-Seq
PCR
immunoprecipitation
ChIP
pull-down
protein assay
ELISA
ELISAs
glycosylation

Software Mentioned

UCSC Genome Browser
Aperio ImageScope
NIH DAVID
COR
Pyro Q - CpG
R
Kallisto
LI

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