PDGFRα expression induces dedifferentiation in thyroid cancer cells by disrupting nuclear TTF1 protein expression. (a) Western blot of thyroid cancer cell lines KTC1, BHT101, BCPAP, TPC1, 8305C, and SW579 demonstrate an inverse relationship between PDGFRα and TTF1 expression. NT: normal thyroid primary culture control. (b) Western blot of BCPAP cells with inducible expression of PDGFRα under a doxycycline promoter disrupts TTF1 expression. BCPAP cells transduced with empty vector as a control (mock). (c) Western blot demonstrating that expression, or selective knockdown, of PDGFRα in TPC1 cells disrupts or restores, TTF1 expression. This effect is not altered by the presence of PDGFRβ. Cells transduced with non-effective shRNA cassette as control (mock). (d) Selective knockdown of PDGFRα in dedifferentiated thyroid cancer cell line 8305C restores TTF1 expression. (e) mRNA screen comparing patient matched primary tumors and metastatic disease. (f) Quantitative analysis using flow cytometry of freshly isolated primary tumors comparing PDGFRα positive cells in primary tumors lacking metastases (n = 4) with proven metastatic disease (n = 6), results are means ± SEM.