IFI16: A Novel Growth Suppressor in Human Prostate Cancer
HX Bui, JP Reynolds, GA Hill, R Panchananthan, D Choubey. VAMC and U of Cincinnati, Cincinnati, OH
Background: Tumor suppressors (TS) provided a molecular basis for multistep carcinogenesis; human cancers have multiple genetic alterations including loss of TS. Interferon inducible IFI16 (encoded by IFI16 gene) is a human member of the p200-protein family and its increased expression in human normal prostate epithelial cells (PrECs) leads to cellular senescence-associated cell growth arrest. Our aim is to study the role of IFI16 protein in PC, as studies of TMPRSS2 overexpression predict aggressive PC.
Design: By immunoblotting, expression of IFI16 protein was compared in total cell lysates from cultured normal PrEC, a benign prostate hyperplasia cell line (BPH-1), and derivatives from the BPH1 cell line that have acquired the ability to form tumors in nude mice (aggressive lines), and PC cell lines (RWPE-1, DU-145, PC-3 and LNCaP). Human prostate tissue array slides (Imgenex) containing 98 prostate samples and 30 of our own archival cases (total 45 BPH, 29 Gleason Score(GS)>6, 26 GS7, 24 GS<8, and 4 metastatic PC to bone marrow and lymph nodes) were stained with H&E and IHC for IFI16 (goat polyclonal sc-6050 Santa Cruz Biotech) and p63 (Ventana pre-dilute). Two pathologists independently reviewed and concurred on GS and IHC intensity and percentage of glands staining for IFI16 on a scale of 0 (no stain) to 2 (highest). Expression of p63 was used as a control in cell cultures and tissue IHC.
Results: Normal PrEC and BPH cell lines expressed IFI16 protein; however, IFI16 is reduced or lost in more aggressive BPH1 and most human PC cell lines tested. P63 was lost in all PC cells and tissue, as a control.
IHC expressed IFI16 weakly in BPH, and strongly in low grade PC; most high grade PC and metastasis lost the IFI16 staining. P=0.0003.
IHC for IFI16 number of cases (% of cases)
Conclusions: This study shows molecular and phenotypic evidence that IFI16 loss may serve as a late hit in the multistep carcinogenesis of PC. Our model shows loss of IFI16 expression in higher grade/stage PC; this may predict aggressive PC, similar to TMPRSS2 overexpression. Further studies are warranted to confirm our findings.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 93, Wednesday Morning