Discussion Medullary thyroid cancer is an indolent neuroendocrine tumor that frequently presents

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Discussion Medullary thyroid cancer is an indolent neuroendocrine tumor that frequently presents with disseminated disease. While locally advanced tumor in the neck and mediastinum can be treated with surgery either for palliative or curative intent, distant metastases are not often amenable to operative excision. Metastatic MTC has a similarly poor response to radiotherapy and chemotherapy. Viable therapeutic options for distant metastatic disease are still absent. Survival rate after discovery of distant metastasis has been around 25% at 5 years and 10% after 10 years, though this has more recently been improved due to earlier discovery of the malignancy (12, 13). However, new molecular targets have expedited the oncologic research…show more content…
It may act as tumor promoter or tumor suppressor depending on the cell milieu (17). One study suggests that the MEK signaling pathway is vital in the regulation of MTC phenotype (18). In the current work, activation of MEK by doxycycline induction led to an increase in functional MEK protein production in a dose-dependent way. Our results depict that continuous MEK activation in TT-MEK cells inhibited tumor cell growth. Notably, this growth reduction was dependent on the levels of the MEK protein present. We have also demonstrated that activation of MEK in MTC cells reduces the levels of CgA and ASCL1. These findings provide the first documentation of the role of MEK signaling as a tumor suppressor in MTC cells. Activation of the Raf1 signaling pathway has been shown to inhibit growth in SCLC, MTC, and carcinoid cells in vitro (6, 19 ), and we showed that doxycycline-induced MEK expression also led to inhibition of cell growth in MTC cells. Taken together, these results suggest that components of the MEK signaling pathway tightly regulate the MTC phenotype. Raf-1 activation in MTC cells also leads to significant reductions in the production of tumor markers CgA and ASCL1. The findings of this study demonstrate a reduction of ASCL1 and CgA with MEK activation. At the same time, we observed similar morphological changes with both raf-1 activation and MEK activation in MTC cells, where MTC cells with either of these proteins

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