Activation of ERK/IER3/PP2A-B56 gamma-positive feedback loop in lung adenocarcinoma by allelic deletion of B56 gamma gene

作者：Ito Tomoko; Ozaki Satoru; Chanasong Rachanee; Mizutani Yuki; Oyama Takeru; Sakurai Hiroshi; Matsumoto Isao; Takemura Hirofumi; Kawahara Ei^*

来源：Oncology Reports, 2016, 35(5): 2635-2642.

DOI：10.3892/or.2016.4677

• immediate early response gene 3
• extracellular signal-regulated kinase
• PP2A
• B56 gamma
• deletion
• non-small cell lung cancer

In order to investigate the involvement of the IER3/PP2A-B56 gamma/ERK-positive feedback loop, which leads to sustained phosphorylation/activation of ERK in carcinogenesis, we immunohistochemically examined the expression of IER3 and phosphorylated ERK in lung tumor tissues. IER3 was overexpressed in all cases of adenocarcinomas examined, but was not overexpressed in squamous cell carcinomas. Phosphorylated ERK (pERK) was also overexpressed in almost all adenocarcinomas. EGFR and RAS, whose gene product is located upstream of ERK, were sequenced. Activating mutation of EGFR, which is a possible cause of overexpression of IER3 and pERK, was found only in 5 adenocarcinomas (42%). No mutation of RAS was found. We further examined the sequences of all exons of B56 gamma gene (PPP2R5C) and IER3, but no mutation was found. Using a single nucleotide insertion in intron 1 of PPP2R5C, which was found in the process of sequencing, allelic deletion of PPP2R5C was examined. Eight cases were informative (67%), and the deletion was found in 4 of them (50%). Three cases having deletion of PPP2R5C did not have EGFR mutation. Finally, PPP2R5C deletion or EGFR mutation that could be responsible for IER3/pERK overexpression was found in at least 8 cases (67% or more). This is the first report of a high incidence of deletion of PPP2R5C in human carcinomas.

• 出版日期2016-5