Transcription profiling of human intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue

ABSTRACT: Papillary thyroid cancers (PTC) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison to the central regions of primary PTCs, the invasive fronts overexpressed TGF ï€� ï€¬ï€� NFb and integrin pathway members, and regulators of small G-proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 35 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required for the development and maintenance of both a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is a common mechanism of PTC invasion and that vimentin regulates thyroid cancer EMT in vitro. Experiment Overall Design: Total RNA was obtained from all 7 central and invasion regions, as well as from 4 of 7 normal tissues. In addition, the comparison of central vs. normal tissues were compared to 9 paired central and normal samples from The Ohio State University tumor bank simultaneously analyzed using the same methods

ORGANISM(S): Homo sapiens

SUBMITTER: Sandya Liyanarachchi 

PROVIDER: E-GEOD-6004 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress