Ciencia y terapia del cáncer

Elevated Serum Antibody Levels against Cyclin L2 in Patients with Esophageal Squamous Cell Carcinoma

Abstract

Hideaki Shimada, Masaaki Ito, Akiko Kagaya, Tooru Shiratori, Mari Kuboshima, Masae Suzuki, Tian-Ling Liu, Yoshihiro Nabeya, Hisahiro Matsubara, Kazuyuki Matsushita, Fumio Nomura, Masaki Takiguchi and Takaki Hiwasa

Cyclin L2 (CCNL2) (Acc. No.: NM_030937) was detected as a tumor antigen of esophageal squamous cell carcinoma (SCC) by serological identification of antigens by recombinant cDNA expression cloning (SEREX). Serum anti-CCNL2 antibodies were detected by enzyme-linked immunosorbent assay more frequent in patients with esophageal SCC than in healthy donors (32% and 15%, P<0.01). An AlphaLISA further confirmed the significant difference in serum antibody levels between the patients and healthy donors using a different set of serum specimens. The expression levels of CCNL2 mRNA detected by reverse transcription polymerase chain reaction were higher in esophageal SCC tissues than those detected in adjacent normal esophageal tissues. We then analyzed for biological function by the transient transfection of CCNL2 expression plasmids into ras-NIH3T3 mouse fibroblasts followed by analysis via luciferase assay using p53-responsive reporter plasmids. CCNL2 increased the transactivation ability of p53, which was attenuated by protein kinase C (PKC) inhibitors or a dominant negative PKCa. Thus, it is possible that CCNL2 activates p53 via PKCa activation.