Seong, Chan Ying
(2012)
Effect of phorbol 12-myristate 13-acetate treatment on
choline kinase expression.
Project Report.
Universiti Sains Malaysia.
(Submitted)
Abstract
Choline kinase (CK) plays main role in the de novo phospholipid synthesis
pathway. It phosphorylates choline into phosphocholine in the presence of
ATP and Mg2*. Many studies have showed that the carcinogenesis and
tumorigenesis are associated with the increased of CK and it has become the
hallmark of cancerous cells. It is so importantly that CK has become the
potential target of the anti-cancer therapy. Yet, studies on the promoter
sequence of the CK remain rare. In order to identify the potential transcription
factor binding sites which act on regulating the CK promoter, -1252 to -1275
of choline kinase a, (hCKa) promoter sequence was investigated for the
effect of phorbol 12-myristate 13-acetate (PMA) treament in human breast
adenocarcinoma cell lines, MCF-7. A -1284 putative promoter of CKa was cloned into a luciferase (Luc) based
reporter vector system. In MCF-7 cells, PMA treatment decreased the
expression of Luc under the control of the CKa promoter. In addition, CKa
mRNA and protein levels were decreased compare to the control in response
to the PMA treatment. PMA, the protein kinase C (PKC) activator, promoted
the E26 transformation specific sequencec, Ets family transcription factors
activity. The results suggest that cEts family transcription factors were acting
as negative regulators of CKa promoter activity.
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