Differentiation of medullary thyroid cancer by C-Raf-1 silences expression of the neural transcription factor human achaete-scute homolog-1

摘要: Background. Human achaete-scute homolog-1 (hASH1), a fetal neural transcription factor, is highly expressed in neuroendocrine tumors such as medullary thyroid cancer (MTC). Although hASH1 probably plays part the growth and development of these tumors, its precise role mechanism are unknown. Methods. To further elucidate function regulation tumor differentiation, we used model MTC differentiation mediated by ras/raf-1 signaling pathway. The TT cells alone or transduced with β-estradiol activatable raf-1 construct (TT:ΔRaf-1:ER) were treated carrier. Northern analysis nuclear run-off assays performed to determine messenger RNA (mRNA) levels rate, respectively. Results. TT:ΔRaf-1:ER underwent marked biochemical morphologic changes, including cell rounding, increase calcitonin transcription, loss RET proto-oncogene expression, cessation growth. During this process expression mRNA was silenced. Nuclear experiments revealed that decrease steady-state activation resulted predominantly from transcriptional inhibition. Conclusions. Silencing parallel associated mature C-cell pattern. Mechanisms leading silencing may be crucial regulating proliferative capacity status MTC. Downstream targets could play proliferation progression