Studies of the Expression Profiles and Regulatory Mechanisms of the Lewis- and I-Antigen Related Genes in Cell Differentiation Models
Date Issued
2005
Date
2005
Author(s)
DOI
zh-TW
Abstract
Changes of structure and expression profile of cell surface carbohydrates are often
observed in the tumorigenesis. For example, sialyl Lewis a (sLea) and sialyl Lewis x
(sLex) epitopes, well known cancer-associated antigens, increased in colorectal
cancerous tissues. Lewis antigens have been known building on a poly-LacNAc
(Galβ1-3/4GlcNAcβ-, LacNAc) backbone structure, which can be divided into type 1
(Galβ1-3GlcNAcβ-) and type 2 (Galβ1-4GlcNAcβ-) chains. Linear poly-LacNAc
structure called i antigen, whereas the branched one called I antigen. The expression
pattern of Ii antigens is developmentally regulated and altered during oncogenesis.
The molecular mechanism, which leads to cancer-associated expression of sialyl
Lewis x/a and the roles of the branched I-antigen structure and I gene in the formation
of multimeric Lewis antigen structure have not been well understood. The main study
divided into two parts, the first one is establishment of enterocytic differentiation
model in Caco-2 cell, and profiling the expression of Lewis- and I-related genes. The
second is regarding the regulatory mechanism of I gene in Caco-2 and K562
differentiation models.
We have profiled the expression of β3GalT5, FUT1, FUT2, FUT3, FUT6, FUT7,
and I genes before and after the differentiation of Caco-2 cells. We observed that the
increment of H type 1 antigens after Caco-2 cell differentiated is due to the enhanced
expression of upstream β3GalT5 gene. FUT3 and FUT6 genes are highly expressed at
transcriptional level after Caco-2 cell differentiated, but the amount of Lewis antigens
is not increased. Further investigation is worth doing.
As significant down-regulation of IGnTC gene in differentiated Caco-2 cell, we
established another K562 cell differentiation model, which IGnTC was up-regulated,
to study the regulation mechanism of IGnTC gene. However, the regulatory elements
of IGnTC gene in these two cell models are quite different. The possible regulatory
element appears to locate on 5’ -2572~-1066 region in Caco-2 cells, whereas in K562
cells the regulatory element of IGnTC gene appears to locate on 5’ -318~-251 region.
The sequence of the -318~-251 region contains the potential binding sites for
transcription factors Oct-2.1, Sp1 and C/EBPα.
Subjects
醣抗原
細胞分化模型
Lewis antigen
I antigen
Caco-2
SDGs
Type
other