The Role and Expression Pattern of TET1 in Breast Cancer
Date
2019-12-18
Authors
Mahmoud Ali Mousa Al-Zahayqa
محمود علي موسى الزحايقة
Journal Title
Journal ISSN
Volume Title
Publisher
Al-quds university
Abstract
Cancer is a genetic disease. Mutations and epigenetic alterations such as aberrant DNA
methylation which results in altered gene expression is evident in all cancers studied, and
is likely responsible for its major hallmarks. Methylation is maintained by DNA
methyltransferases, however, methylation can be reversed by mechanisms that are poorly
understood. Recently, functional demethylation was linked to hydroxylation of 5hmC by
the TET family. TET1 is the most reduced member in a variety of human malignancies,
suggesting a tumor suppressor function for this protein. In addition, published research
showed controversial conclusions about TET1 function in breast cancer. Moreover,
recent evidence showed that TET1 has more than one isoform. Thus, our hypothesis
proposes the different TET1 isoforms may play different roles in breast cancer through
differential expression pattern in different transformation contexts. In the present study,
we tested the expression level and localization of TET1 enzyme in breast cancer samples
using IHC, and the expression level using relative qRT-PCR in different breast cancer
cell lines under different contexts. In addition, we tested the expression pattern of
different TET1 isoforms using in vitro and in vivo cell transformation models. We also
tested the effect of TET1 overexpression in MDA MB231 cells using lentivirus vector
containing TET1 coding sequence on various cancer hallmarks. Our results demonstrate
that TET1 has differential expression pattern in breast cancer embedded tissue samples
compared to normal tissue. In addition, TET1 expression correlated with the
differentiation level. From our hormone experiments, and in vitro as well as in vivo
transformation studies, we clearly showed that different TET1 isoforms are differentially
expressed under different physiological and transformation contexts, and different TET1
isoforms having different distribution pattern. Finally, we proved that TET1 full length is
a tumor suppressor gene. In conclusion, our study demonstrates the role of TET1 in
breast cancer is not straight forward one and this necessitates future studies to better
characterize the TET1 function in breast cancer initiation and progression