Chong Susan DSR 610 Final
Susan Chong
DSR 610
6 May 2015
EZH2 and Notch1 signaling in glioblastomas and breast cancer stem cells
Within a tumor exists a subpopulation of cells that present less abnormal characteristics; however, there exists another type that hold the potential to recreate and expand tumor mass.
The latter share similar characteristics to normal stem cells, which are the unlimited ability to self-renew and the ability to maintain undifferentiated. Over the course of time, these cells will differentiate into tumor stem cells (TSC) or tumor-initiating cells with stem-like properties (TICs).
Researchers previously identified TICs in glioblastomas and confirmed that TICs share functional similarities to neural stem cells (NSCs). A similarity is that, in both cell types, BMP is a key inhibitor regulatory of TICs from glioblastomas. On the other hand, a difference is that
TICs undergo genetic aberrations that are similar to tumors, which in turn give rise to the typical tumor phenotype [1]. What still remains unknown is during which point in the developmental process in tissues do TICs form and also what are the intrinsic cell signaling pathways that are disrupted in TICs.
To answer this, they looked into the potential aberrant methylation in the BMPR1B promoter in 0308-TIC cell line. Bisulfite treating the DNA in 0308 cells showed that the CpG islands are normally heavily methylated. However, this can be reversed by treating cells with 5Azacytidine (5’azaC). First studied in 1979 by fellow USC researchers, 5’azaC is an FDAapproved chemotherapeutic agent that is also a DNA methylation inhibitor [4]. By forcing demethylation in 0308 cells, there was a significant increase in BMPR1B mRNA expression, suggesting that the control or untreated 0308-TICs do not typically express BMPR1B [1].
Furthermore, the enhancer of zeste homolog 2 (EZH2) is a key component of the polycomb repressive complex 2 (PCR2). Together, they facilitate methylation and are highly
expression in tumor cells
DSR 610
6 May 2015
EZH2 and Notch1 signaling in glioblastomas and breast cancer stem cells
Within a tumor exists a subpopulation of cells that present less abnormal characteristics; however, there exists another type that hold the potential to recreate and expand tumor mass.
The latter share similar characteristics to normal stem cells, which are the unlimited ability to self-renew and the ability to maintain undifferentiated. Over the course of time, these cells will differentiate into tumor stem cells (TSC) or tumor-initiating cells with stem-like properties (TICs).
Researchers previously identified TICs in glioblastomas and confirmed that TICs share functional similarities to neural stem cells (NSCs). A similarity is that, in both cell types, BMP is a key inhibitor regulatory of TICs from glioblastomas. On the other hand, a difference is that
TICs undergo genetic aberrations that are similar to tumors, which in turn give rise to the typical tumor phenotype [1]. What still remains unknown is during which point in the developmental process in tissues do TICs form and also what are the intrinsic cell signaling pathways that are disrupted in TICs.
To answer this, they looked into the potential aberrant methylation in the BMPR1B promoter in 0308-TIC cell line. Bisulfite treating the DNA in 0308 cells showed that the CpG islands are normally heavily methylated. However, this can be reversed by treating cells with 5Azacytidine (5’azaC). First studied in 1979 by fellow USC researchers, 5’azaC is an FDAapproved chemotherapeutic agent that is also a DNA methylation inhibitor [4]. By forcing demethylation in 0308 cells, there was a significant increase in BMPR1B mRNA expression, suggesting that the control or untreated 0308-TICs do not typically express BMPR1B [1].
Furthermore, the enhancer of zeste homolog 2 (EZH2) is a key component of the polycomb repressive complex 2 (PCR2). Together, they facilitate methylation and are highly
expression in tumor cells
References: (2008): 69-80. Web. America 111.8 (2014): 3098–3103. PMC. Web. neurosurgery 131.0 (2015): 54-8. Web. Cells Treated with 5-Azacytidine." Cell 17.4 (1979): 771-9.