A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer.
We examined a possible application of regulatory regions of the midkine (MK) gene for suicide gene therapy of pancreatic cancer. The expression of MK has been demonstrated in human pancreatic cancer tissues but scarcely in normal adult tissues. Northern blot analysis confirmed that human pancreatic cancer cell lines expressed the MK gene. A 609-bp genomic fragment in the 5'-regulatory region of the MK gene, when transfected into human pancreatic cancer cells, activated the transcription of a fused reporter gene to an extent greater than the SV40 promoter. In contrast, the 609-bp fragment-mediated promoter activity tested in fibroblast cells was significantly weak. Human pancreatic cancer cells (AsPC-1) that were transduced with the herpes simplex virus-thymidine kinase gene linked with the 609-bp promoter markedly increased their sensitivity to a prodrug, ganciclovir, compared with untransduced cells. The present study suggests that preferential cytotoxic effects for pancreatic tumors can be achieved by using the MK promoter.
Yoshida
Yu
Y
Division of Pathology, Chiba Cancer Center Research Institute, Japan.
Tomizawa
Minoru
M
Bahar
Rumana
R
Miyauchi
Motohiro
M
Yamaguchi
Taketo
T
Saisho
Hiromitsu
H
Kadomatsu
Kenji
K
Muramatsu
Takashi
T
Matsubara
Shuichiro
S
Sakiyama
Shigeru
S
Tagawa
Masatoshi
M
D002352:Carrier Proteins / Q000235:genetics*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D016207:Cytokines; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D000078792:Midkine; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D016207:Cytokines; D000078792:Midkine; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase; D015774:Ganciclovir