Abstract
Protein interacting with carboxyl terminus 1 (PICT-1) is a nucleolar protein shown to act as a tumor suppressor that interacts with PTEN, or in a contrasting manner to facilitate the accessibility of p53 to ubiquitination and degradation, thus to function as an oncogene. The aim of the study was to examine the potential role of PICT-1 in neuroendocrine neoplasm (NEN) tumorigenesis and response to mTOR inhibitor treatment. PICT-1 was overexpressed in medullary thyroid (TT) and pancreatic (BON1) NEN cell lines using lentiviral vector. Whereas in BON1 cells PICT-1 overexpression exhibited no significant impact, in TT cells it induced the appearance of p53β lacking the C-terminus end. This was accompanied by a robust decrease in p21 expression and elevation of cell viability. Remarkably, PICT-1 overexpression completely reversed the reduction in cell viability of medullary thyroid neoplasm cells induced by everolimus, a therapeutic option for patients with progressive NENs. mTOR pathway investigations revealed that PICT-1 overexpression induced a reduction in PTEN expression and a robust increase in the expression level of phospho-Akt-Ser47 only partially inhibited by everolimus. These findings suggest a possible role of PICT-1 in the spliceosome machinery and provide functional involvement of PICT-1 in the complex network of mTOR.