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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.

Tomizawa M, Yu L, Wada A, Tamaoki T, Kadomatsu K, Muramatsu T, Matsubara S, Watanabe K, Ebara M, Saisho H, Sakiyama S, Tagawa M - Br. J. Cancer (2003)

Bottom Line: In contrast, three HCC specimens and one corresponding noncancerous sample out of the three AFP-positive HCC cases expressed the AFP gene.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology, Chiba Cancer Center, 666-2, Nitona, Chuo-ku, Chiba 260-8717, Japan.

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.

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Related in: MedlinePlus

Susceptibility of HuH-7 (A), PLC/PRF/5 (B), HLE (C), HLF (D), MCF-7 (E) and AsPC-1 (F) cells to various concentrations of GCV. Parent cells and G418-resistant cells that were transfected with vector, MK2.3-TK or AFPEn0.2-TK DNA were used. Standard error bars are also shown.
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fig3: Susceptibility of HuH-7 (A), PLC/PRF/5 (B), HLE (C), HLF (D), MCF-7 (E) and AsPC-1 (F) cells to various concentrations of GCV. Parent cells and G418-resistant cells that were transfected with vector, MK2.3-TK or AFPEn0.2-TK DNA were used. Standard error bars are also shown.

Mentions: We compared increased cytotoxic activity caused by the HSV-TK/GCV system using the MK and the AFP promoters. All the cells were transfected with MK2.3-TK, AFPEn0.2-TK or vector DNA and then respective G418-resistant cells were exposed to various concentrations of GCV (Figure 3Figure 3


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.

Tomizawa M, Yu L, Wada A, Tamaoki T, Kadomatsu K, Muramatsu T, Matsubara S, Watanabe K, Ebara M, Saisho H, Sakiyama S, Tagawa M - Br. J. Cancer (2003)

Susceptibility of HuH-7 (A), PLC/PRF/5 (B), HLE (C), HLF (D), MCF-7 (E) and AsPC-1 (F) cells to various concentrations of GCV. Parent cells and G418-resistant cells that were transfected with vector, MK2.3-TK or AFPEn0.2-TK DNA were used. Standard error bars are also shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376946&req=5

fig3: Susceptibility of HuH-7 (A), PLC/PRF/5 (B), HLE (C), HLF (D), MCF-7 (E) and AsPC-1 (F) cells to various concentrations of GCV. Parent cells and G418-resistant cells that were transfected with vector, MK2.3-TK or AFPEn0.2-TK DNA were used. Standard error bars are also shown.
Mentions: We compared increased cytotoxic activity caused by the HSV-TK/GCV system using the MK and the AFP promoters. All the cells were transfected with MK2.3-TK, AFPEn0.2-TK or vector DNA and then respective G418-resistant cells were exposed to various concentrations of GCV (Figure 3Figure 3

Bottom Line: In contrast, three HCC specimens and one corresponding noncancerous sample out of the three AFP-positive HCC cases expressed the AFP gene.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology, Chiba Cancer Center, 666-2, Nitona, Chuo-ku, Chiba 260-8717, Japan.

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.

Show MeSH
Related in: MedlinePlus