BRAFV600E promotes invasiveness of thyroid cancer cells through nuclear factor kappaB activation.

The BRAFV600E mutation is closely linked to tumorigenesis and malignant phenotype of papillary thyroid cancer. Signaling pathways activated by BRAFV600E are still unclear except a common activation pathway, MAPK cascade. To investigate the possible target of BRAFV600E, we developed two different cell culture models: 1) doxycycline-inducible BRAFV600E-expressing clonal line derived from human thyroid cancer WRO cells originally harboring wild-type BRAF; 2) WRO, KTC-3, and NPA cells infected with an adenovirus vector carrying BRAFV600E.

Selective pharmacologic inhibition of c-Jun NH2-terminal kinase radiosensitizes thyroid anaplastic cancer cell lines via induction of terminal growth arrest.

Context: The high radioresistance of anaplastic thyroid cancer (ATC) and cultured ATC cells stipulates for the means of increasing their radiosensitivity. It has been shown that c-Jun NH(2)-terminal kinase (JNK) activation is one of the manifestations of radiation response in ATC cells.

Objective: Assessment of the effect of selective JNK inhibition on ATC cell radiosensitivity and clarification of the associated mechanisms.

Radiation-induced senescence-like terminal growth arrest in thyroid cells.

Premature senescence may play an important role as an acute, drug-, or ionizing radiation (IR)-inducible growth arrest program along with interphase apoptosis and mitotic catastrophe. The aim of the study was to evaluate whether IR can induce senescence-like phenotype (SLP) associated with terminal growth arrest in the thyroid cells, and if so, to evaluate impact of terminal growth arrest associated with SLP in intrinsic radiosensitivity of various thyroid carcinomas. The induction of SLP in thyroid cells were identified by: (1) senescence associated beta-galactosidase (SA-beta-Gal) staining method, (2) dual-flow cytometric analysis of cell proliferation and side light scatter using vital staining with PKH-2 fluorescent dye, (3) double labeling for 5-bromodeoxyuridine and SA- beta-Gal, (4) Staining for SA-beta-Gal with consequent antithyroglobulin immunohistochemistry.

The selective tyrosine kinase inhibitor, STI571, inhibits growth of anaplastic thyroid cancer cells.

To establish a molecular targeting therapy for anaplastic thyroid carcinomas, we studied the effect of the specific tyrosine kinase inhibitor, STI571, on anaplastic thyroid cancer cell lines highly expressing c-ABL ARO (mutated p53) and FRO (undetectable p53). These lines showed marked inhibition of cell growth after treatment with STI571. In contrast, the growth of papillary thyroid cancer cell lines that harbor wild-type p53 and have low levels of c-ABL was not affected by STI571.