Abstract 4334: Expression of PID1 correlates with PFS in pediatric medulloblastomas and negatively impacts growth of medulloblastoma, glioblastoma and AT/RT brain tumor cell lines

Abstract

PID1, discovered in 2006, encodes an adapter protein that contains a phosphotyrosine binding (PTB) domain. Overexpression of PID1 can have inhibitory or proliferative effect, depending on the cell line. In adipocytes and myocytes PID1 inhibits insulin-induced signaling via a yet-unknown mechanism. To date, there are no reports on PID1 effects in cancer. Using quantitative real time RT-PCR of PID1 expression in 78 pediatric medulloblastoma tumors at diagnosis we found that higher PID1 expression correlated with longer progression-free survival (PFS) in multivariate analysis. Similar correlation was found for PID1 variant 1 and variant 2. Interestingly, PID1 was higher in desmoplastic medulloblastomas, which carry better prognosis vs. anaplastic medulloblastomas, which have poorer prognosis. Query of the REMBRANDT database showed that higher PID1 expression was highly correlated with longer overall survival (OS) in gliomas. REMBRANDT also showed that PID1 expression in GBMs (n=228) was 0.47 of the PID1 expression in non-tumor brain (n=28) (p<0.001) and similarly, was lower in GBMs compared to astrocytoma II/III or oligodendroglioma. TCGA similarly showed that PID1 expression in GBM was 0.40 of its expression in non-tumor brain. In tissue culture we found that transient transfection of PID1-tGFP, but not tGFP, inhibited colony formation in GBM (U251, LN229), medulloblastoma (D283MED) and ATRT (CHLA-06-ATRT) cell lines. PID1 expression decreased proliferation (BrdU, 7AAD), increased sub-G0/G1, increased apoptosis (AnnexinV), and increased mitochondrial depolarization (JC1 probe) of GBM, medulloblastoma and/or ATRT cell lines, supporting an inhibitory function for PID1 in these tumors. Studies are currently ongoing into the molecular mechanism that mediates these effects. In summary, our data demonstrate correlation between high PID1 expression and better patient outcome in two different brain tumors: medulloblastomas and gliomas, and inhibitory effect of PID1 in three types of brain tumor cell lines: medulloblastomas, gliomas, and ATRT. This suggests that PID1 may have a functional role in the biology, and possibly in response to therapy, of these three brain tumor types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4334. doi:1538-7445.AM2012-4334