title: The thyroid cancer PAX8-PPARG fusion protein activates Wnt/TCF-responsive cells that have a transformed phenotype.
abstract: A chromosomal translocation results in the production of a paired box 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARG) fusion protein (PPFP) in ∼35% of follicular thyroid carcinomas. To examine the role of PPFP in thyroid oncogenesis, the fusion protein was stably expressed in the non-transformed rat thyroid cell line PCCL3. PPFP conferred on PCCL3 cells the ability to invade through Matrigel and to form colonies in anchorage-independent conditions. PPFP also increased the fraction of cells with Wnt/TCF-responsive green fluorescent protein reporter gene expression. This Wnt/TCF-activated population was enriched for colony-forming and invading cells. These actions of PPFP required a functional PPARG DNA binding domain (DBD) within PPFP and were further stimulated by PPARG agonists. These data indicate that PPFP, through its PPARG DBD, induces Wnt/TCF pathway activation in a subpopulation of cells, and these cells have properties of cellular transformation including increased invasiveness and anchorage-independent growth.
authors.affiliation: Cellular and Molecular Biology Graduate Program, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, 48109, USA.
authors.forename: Dang
authors.initials: D
authors.lastname: Vu-Phan
authors.forename: Vladimir
authors.initials: V
authors.lastname: Grachtchouk
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Yu
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Colby
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Koenig
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010641:Phenotype; D000077205:Pioglitazone; D051381:Rats; D051820:TCF Transcription Factors / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D015514:Oncogene Proteins, Fusion; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D051820:TCF Transcription Factors; D045162:Thiazolidinediones; D051153:Wnt Proteins; D000077205:Pioglitazone
keywords: PPFP; TCF; Wnt; thyroid carcinoma
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