Past Issue

Volume 12, Supplement 1,Winter 2011 (Presented at The 1st International Student Congress) Pages: 15-16

I-20: Oct-4B1: Its Discovery and Function in Stem Cells and Cancers

Oct-4 (also known as POU5F1) is a key regulator of Abstract of the 1st Int. Student Congress on Cell & Molecular Medicine Cell Journal(Yakhteh), Vol 12, Suppl 1, Winter 2011 16 self-renewal in embryonic stem cells. Regarding the new cancer stem cell concept, the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of tumor behavior, such as tumor recurrence or resistance to therapies. Here, we have investigated the potential expression and function of Oct-4 in stem and tumor cell lines as well as tumor and non-tumor biopsy specimens. Oct-4 expression was detected in almost all examined bladder and stomach tumors, but at much lower level in some non-neoplastic samples. Western blot analysis further confirmed the expression of Oct-4 in tumor biopsies. According to IHC results, Oct-4 is localized in both cytoplasm and nuclei of tumor cells, with no or low immunoreactivity in nontumor cells. Oct-4 can potentially encode two spliced variants, designated Oct-4A and Oct-4B. We next examined the expression pattern of these Oct-4 isoforms in various human pluripotent and nonpluripotent cells. Our data revealed that whereas Oct-4A expression is restricted to embryonic stem (ES) and embryonal carcinoma (EC) cells, Oct-4B can be detected in various nonpluripotent cell types. Furthermore, we detected a novel Oct-4 spliced variant, designated Oct-4B1, that is expressed primarily in human ES and EC cells and is downregulated following their differentiation. We further detected the expression of Oct-4B1 in bladder and stomach tumors with no or much lower expression in marginal samples of the same patients. We have also analyzed the effects of Oct-4B1 knock-down in AGS cell line treated with specific siRNA directed toward Oct-4B1. Our data revealed that interfering with the expression of Oct-4B1 caused profound changes in the morphology and cell cycle distribution of the cells. Furthermore, down-regulation of Oct-4B1 significantly elevated the relative activity of caspase-3/caspase-7 and the rate of apoptosis in the cells. All together, our findings suggest that Oct-4B1 has a potential role in tumorigenesis and candidates the variant as a new tumor marker with potential value in diagnosis and treatmen