Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter.
We examined the expression level of the midkine (MK) and c-erbB-2 genes in both tumorous and matched nontumorous specimens from 18 patients with breast cancer. Expression of the MK and c-erbB-2 genes in nontumorous regions was relatively low, and the expression levels of both genes were not markedly different among the nontumorous samples. In contrast, the expression of the MK and c-erbB-2 genes in tumorous specimens was upregulated in 18 and 6 specimens, respectively. Regulatory regions of the MK gene were able to activate a reporter gene to a similar degree as those of the c-erbB-2 gene in the human breast cancer cell lines tested. Transfection of breast cancer cells with either the MK promoter- or the c-erbB-2 promoter-linked herpes simplex virus thymidine kinase gene increased their sensitivity to the prodrug ganciclovir. These data showed that the MK promoter activated a therapeutic gene in a wider range of human breast cancer than the c-erbB-2 promoter and suggest that MK promoter-mediated gene therapy is potentially more favorable in clinical settings.
Yu
Ling
L
Division of Pathology, Chiba Cancer Center, Chiba, Japan.
Yamamoto
Naohito
N
Kadomatsu
Kenji
K
Muramatsu
Takashi
T
Matsubara
Shuichiro
S
Sakiyama
Shigeru
S
Tagawa
Masatoshi
M
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D046508:Culture Techniques; D016207:Cytokines; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D041722:Genes, Transgenic, Suicide; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D000078792:Midkine; D011401:Promoter Regions, Genetic / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation
D002352:Carrier Proteins; D016207:Cytokines; D000078792:Midkine; D013937:Thymidine Kinase