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Abstract: The Effect of DNA Methylation on TP73 Expression in Tumorgenesis
Nujuma Moussa, Zhixing Yao, Zaki A. Sherif
Department of Biochemistry & Molecular Biology, Howard University College of Medicine
TP73 is a member of the TP53 family of proteins that acts as a transcription factor to help regulate cellular distress. This tumor protein may play a dual role as a tumor suppressor and tumor promoter. The TP73 gene is mapped to chromosome 1p36, a frequently deleted region in neuroblastoma and other types of tumors. While mutations in the TP53 gene are commonly known to cause noxious cancers, 30% of cancers result from the overexpression of TP73. In our lab, we examined the role of TP73 in the formation of neuroblastoma, a type of cancer that begins in the nerve tissue atop the adrenal gland of kidneys in children. Normal fibroblast cell lines (HS27) and tumor kidney cells (IMR32 and SK-N-SH) were grown in their respective growth media. DNA and RNA of both cell types were extracted using standard procedures. RNA expression was analyzed by RT-PCR and DNA methylation was analyzed by bisulfite sequencing. The expressions of TP73 gene and its protein were analyzed by gel electrophoresis and immunohistochemistry respectively. We found that the TP73 gene was expressed in all of the neuroblastoma cells, but there was no evidence of its expression in the normal cell lines. Subsequent methylation studies revealed that TP73 was expressed in neuroblastoma cells but not in non-cancerous cells due to silencing by DNA methylation. In conclusion, the absence of TP73 in normal cells is in part due to DNA methylation implying that TP73 plays a role in the promotion and/or progression of carcinogenesis.
cancer, neuroblastoma, epigenetics, methylation, tp73, tp53, tumorgenesis, gene expression
Genetic Processes | Medical Biochemistry | Medical Cell Biology | Oncology
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Dr. Sherif Zaki
Dr. Zhixing Yao
© The Author(s)
Yao, Z. and Sherif, ZA (2016). The effect of epigenetic silencing and TP53 mutation on the expression of DLL4 in human cancer stem disorder. Oncotarget, 7: 62976-62988. doi: 10.18632/oncotarget.11316. Sherif, Z. A., Danielsen, M. (2006). Balanced t(11;15)(q23;q15) in a TP53+/+ breast cancer patient from a Li-Fraumeni syndrome family. Cancer Genetics and Cytogenetics, 168: 50-58.
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