Piwil2-Like Proteins Are Expressed in Precancerous Stem Cells and Various Types of Cancers and Can Regulate Tumor Development
G He, RL Shen, Q Zhou, L Chen, Y Ye, C Shapiro, SH Barsky, JX Gao. Ohio State University, Columbus, OH; Soochow University, Suzhou, Jiangsu, China
Background: Piwil2, a member of AGO/PIWI family proteins, which is silenced in adult tissues has been implicated to play an important role in tumor development. However, the mechanism underlying piwil2 regulating tumor development is largely unknown. Our previous studies have suggested that piwil2-like (PL2L) proteins might regulate precancerous stem cell (pCSCs) development. Herein, we demonstrated that PL2L proteins are expressed in various types of cancers and can regulate tumor development.
Design: First, piwil2-specific Gene-Exon-Array (GEA) RT-PCR was developed to determine the existence of piwil2-like (PL2L) protein transcripts. Then, bioinformatics was used to design a peptide shared by piwil2 and PL2L proteins, which was used to generate polyclonal (pAbs) and monoclonal antibodies (mAbs). Both pAbs and mAbs are able to recognize full length piwil2 and at least four PL2L proteins of human and mouse, including PL2L80, PL2L60, PL2L50, and PL2L40. By using the unique antibodies, we investigated the function of PL2L proteins in tumor developments and their clinic-pathological significance.
Results: A number of piwil2-like (PL2L) proteins, including PL2L80, PL2L60, PL2L50, and PL2L40 have been identified by monoclonal antibodies (mAbs) to piwil2 peptides. Especially, PL2L60 is dominantly and widely expressed in pCSCs and tumor cell lines without the restrictions of tissue origin. The PL2L60 mediated pCSC and tumor cell expansion in vitro is associated with up-regulation of Stat-3 and Bcl-2 genes. Immunohistochemical analysis has revealed that PL2L proteins, rather than piwil2, are ubiquitously expressed in various stages of human primary and metastatic cancers. While PL2L proteins are associated with cancer cell proliferation, piwil2 expression is associated with cancer cell apoptosis.
Conclusions: These findings suggest that piwil2 and PL2L proteins might play important but opposite roles in tumor development and that PL2L proteins might have the potential to be used as a common biomarker for diagnosis, prognosis and effective therapeutic target in early stage of the human cancers.
Category: Pan-genomic/Pan-proteomic Approaches to Diseases
Monday, March 22, 2010 1:00 PM
Poster Session II # 238, Monday Afternoon