TPH1 and pancreatic neuroendocrine tumor: Furthermore, overexpression of NOTCH1 in the human pancreatic endocrine tumour cell line BON1 leads to inhibition of ASCL1 expression, induction of HES1, reduced levels of endocrine markers such as synaptophysin, and also to major repression of TPH1 [12], the rate limiting enzyme in serotonin biosynthesis.