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A promoter region of the midkine gene that is frequently expressed in human hepatocellular carcinoma can activate a suicide gene as effectively as the alpha-fetoprotein promoter.

Abstract：

:We examined the expression of the midkine (MK) and alpha-fetoprotein (AFP) genes in 15 paired human specimens obtained from hepatocellular carcinoma (HCC) and the corresponding noncancerous regions of the same patients. A total of 14 HCC but none of the noncancerous specimens were positive for the MK mRNA. In contrast, three HCC specimens and one corresponding noncancerous sample out of the three AFP-positive HCC cases expressed the AFP gene. A 2.3-kb genomic fragment in the regulatory region of the MK gene could activate a fused reporter gene in both AFP-producing and -nonproducing HCC lines, and the MK fragment-mediated transcriptional activity was comparable to the AFP enhancer-linked AFP promoter in AFP-producing cell lines. The AFP-producing but not AFP-nonproducing HCC cell lines that were transfected with the MK promoter-linked herpes simplex virus-thymidine kinase (HSV-TK) gene became susceptible to a prodrug ganciclovir to a similar degree of the HCC transfected with the enhancer-linked AFP promoter-fused HSV-TK gene. These data suggest that the MK promoter can activate a therapeutic gene preferentially in HCC and is as useful as the AFP promoter in clinical settings.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Tomizawa M,Yu L,Wada A,Tamaoki T,Kadomatsu K,Muramatsu T,Matsubara S,Watanabe K,Ebara M,Saisho H,Sakiyama S,Tagawa M

doi

10.1038/sj.bjc.6601246

subject

Has Abstract

pub_date

2003-09-15 00:00:00

pages

1086-90

issue

6

eissn

0007-0920

issn

1532-1827

pii

6601246

journal_volume

89

pub_type

杂志文章

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