Overexpression of Transcriptional Intermediary Factor 1 Gamma (TIF1γ) and Loss of SMAD4 Are Common Events but Are Not Correlated with Each Other in Pancreatic Ductal Carcinoma
Lili Lee, Martin Ligr, Huamin Wang, Cristina Hajdu, Zhiheng Pei, Ruliang Xu. New York University School of Medicine, New York, NY; The University of Texas, M.D. Anderson Cancer Center, Houston, TX
Background: TIF1γ is a transcriptional cofactor which plays an important role in the regulation of TGFβ pathway through degradation of, or in competition with, Smad4. There is an inverse relationship between expression of TIF1γ and inactivation of Smad4 in in vitro studies. However, it is unclear whether the inverse relationship could also be present in pancreatic ductal carcinomas and how these two factors interact with each other.
Design: We performed Western blot and RT-PCR to confirm the inverse relationship between TIF1γ expression and Smad4 inactivation/loss on three pancreatic cancer cell lines (Panc-1, BxPC-3, and Capan-1) and two immortalized normal pancreatic cell lines (HPDE and HPNE). The relationship between TIF1γ expression and Smad4 inactivation in pancreatic cancer was investigated by immunohistochemistry using tissue microarray prepared from 125 pancreatic cancer resection specimens. Results were analyzed by the Fisher's exact test.
Results: Pancreatic cell lines BxPC-3 and Capan-1 demonstrated the highest TIF1γ expression and lowest Smad4 expression, whereas Panc-1, HPDE, and HPNE had the lowest TIF1γ expression and highest Smad4 expression at both the protein and mRNA levels. In 125 human pancreatic cancer tissue specimens, overexpression of TIF1γ (64%) and loss of Smad4 (53%) were commonevents, but the inverse relationship between them was not evident (P>0.05).
Conclusions: Overexpression of TIF1γ and loss of Smad4 appears to play independent roles in pancreatic carcinogenesis. TIF1γ overexpression, in combination with Smad4 loss, may provide a diagnostic tool for early detection of pancreatic cancer.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 271, Monday Morning