Ps-115: Sex Determining Region Y (SRY) Regulates Cancer-Marker Genes in NTera2 Embryonal Carcinoma Cell Line

Ashrafi Kakhki S *, Favaedi R , Hosseini Salekdeh Gh , Shahhoseini M ,


Objective: The SOX gene family which is characterized by the presence of a conserved DNA-binding high-mobility group (HMG) coding domain, encodes transcription factors that play critical roles in cell fate determination, differentiation and proliferation. Moreover,a number of SOX family members have been recently reported to be silenced in different types of cancer and proposed to act as a tumor suppressor in particular tissues. Sex determining region Y (SRY) is a member of SOX family proteins playing important roles in sex determination by initiating testis development from early bipotential gonads. Although previous studies extremely focused on the molecular mechanism of SRY in testis development,the possible role of SRY in cancer has not been investigated yet. In order to address this question, we looked into possible SRY-regulated genes and their levels of expression in a human embryonic teratocarcinoma cell line, NTera2, before and after onset of differentiation. Materials and Methods: For this respect BCL2 and c-Myc were analyzed as cancer marker genes. Expression levels of c-Myc proto-oncogene and BCL2 at the mRNA level were determined by real time-PCR. Chromatin Immunopercipitation (ChIP) was performed using SRY antibody on chromatin extractions of NTera2 cells before and after differentiation, and SRY incorporation on the regulatory regions of the aforementioned marker genes were evaluated using real time-PCR. Results: The results showed increased incorporation of SRY on the regulatory region of BCL2 and c-Myc after induction of differentiation, parallel with lower expression of these two cancer marker genes. Conclusion: This finding suggests dynamic role of SRY as a transcription repressor for cancer-associated genes in cancer process.