Embryos & Cancer: Oct3/4 Gene & Malignant Phenotype

[iansmith]

Early embryonic pluripotency gene controls malignant phenotype in germ cells | By Cathy Holding

The POU transcription factor Oct3/4 maintains the pluripotent state of inner cell mass cells—at the blastocyst stage of preimplantation development—that develop into the fetus after implantation. Different levels of Oct3/4 expression result in altered potential for a given embryonic cell, and the more pluripotent a cell, the less “mature” it appears in terms of epigenetic programming and gene expression profile. Oct3/4 is also expressed in spermatogonia in the adult male, and levels of expression again are correlated with the “maturity” of that cell.

Germ cell tumors (GCTs) account for a high proportion of malignancy in young men, and in the November issue of Cancer Cell, Sharon Gidekel and colleagues at the Hebrew University Hadassah Medical School report not only that Oct3/4 expression is found almost exclusively in GCTs, but also that the level of expression is related to the immaturity—and hence the malignancy—of the tumor. They also demonstrated for the first time that overexpression of Oct3/4 in a heterologous cell system confers tumorigenicity to that line when it is subsequently injected into nude mice, again with malignancy related to immaturity. Finally, tumor regression was observed when expression levels of Oct3/4 were inhibited. This suggests that Oct3/4 acts as an oncogene and could be a potential therapeutic target for this type of germ cell malignancy (Cancer Cell, 4:361-370, November 2003).

Gidekel et al. used immunohistochemistry and demonstrated the expression of Oct3/4 in all of 45 primary human GCTs and absence in all of 182 solid tumors from other sources. Embryonic stem cell lines previously engineered to have differing inducible levels of Oct3/4 expression were injected into nude mice to assess the effects of varying levels of the gene on tumorigenicity and of induction and repression of expression. Cells were transfected with Oct3/4 expression construct, and tumor-associated properties such as anchorage dependence were tested in the resultant lines.

http://www.biomedcentral.com/news/20031203/02/

 

[Monique]

Well, that is interesting.. how does a transcription factor cause a cell to stay pluripotent? What cascade would be affected.. maybe an inhibitor of differentiation is synthesized?

I wonder what would happen if they specifically would target Oct3/4 for therapy, all our natural stem cells (which are pluri or toti? potent) would start differentiating. Wouldn't such therapy be very toxic? Did they already look for expression of the gene in normal tissues?

I am thinking about bone marrow and basal epithelial cells in particular..

 

[Monique]

Do you know off the top of your head how they found this trancription factor, Ian?

I find it remarkable that they found a trancription factor and not a protein, since transcription factors are present in the cell at very low concentrations..