Ribonucleotide Reductase M2 Subunit Is a Novel Marker and a Potential Therapeutic Target for Gastric Carcinoma
T Morikawa, R Hino, H Uozaki, T Ushiku, T Sakatani, Y Inoue, A Shinozaki, T Nakaya, S Ishikawa, M Fukayama. Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Background: Ribonucleotide reductase M2 subunit (RRM2) is essential for the production of deoxyribonucleotides before DNA synthesis in dividing cells. In some cancer types, RRM2 mRNA expression level correlates with chemoresistance and poor patient outcome. However, there is no information concerning protein expression and the function of RRM2 in gastric carcinoma (GC).
Design: One hundred and fourteen GCs were immunohistochemically analyzed for RRM2 protein expression using a monoclonal antibody for RRM2 and a tissue microarray. The correlations between RRM2 expression and clinicopathological factors were statistically analyzed. To investigate the roles of RRM2 in GC, three GC cell lines, MKN-1, MKN-7, and SNU-719 (derived from poorly differentiated-, well differentiated-, and Epstein-Barr virus-associated GC, respectively) were transfected with RRM2 small interfering RNA and the effects on cell growth were investigated by MTT assay.
Results: RRM2 protein expression was detected in 52 of 114 GCs (45.6%), whereas it was absent in normal gastric foveolar epithelium. RRM2 expression was positively correlated with muscularis propria invasion (p=0.0002), venous invasion (p=0.0012), lymphatic invasion (p=0.034), and lymph node metastasis (p=0.037). Knockdown of the RRM2 expression by small interfering RNA resulted in decreased cell growth in all three GC cell lines investigated.
Conclusions: We demonstrated that RRM2 protein expression was correlated with the malignant potential of GC and that RRM2 had an important role in GC cell growth. Taken together, RRM2 is a novel diagnostic/prognostic marker and a potential therapeutic target molecule for GC.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 108, Tuesday Afternoon