Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

Ishikawa, Hiroki; Nakata, Keisuke; Mawatari, Fumihiro; Ueki, Tetsuya; Tsuruta, Shotaro; Ido, Akio; Nakao, Kazuwa; Kato, Yukio; Ishii, Nobuko; Eguchi, Katsumi

doi:10.1038/sj.gt.3300870

Cited by 38 publications

(20 citation statements)

References 27 publications

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“…Critically, only small amounts of E1a are required for viral replication and so specific but (relatively) weak eukaryotic promoters are not a drawback to the functional efficiency of such CRAd vectors. [Hallenbeck et al, 1999] [Ishikawa et al, 1999] [Kanai, 2001] carcinoembryonic antigen (CEA) CEA-expressing tumours [Brand et al, 1998] [Cao et al, 2001] [Qiao et al, 2002] erbB2 ERBB2-expressing tumours [Vassaux et al, 1999] mucin-1 (muc1) MUC1 (DF3)-expressing tumours [Stackhouse et al, 1999] [ Tai et al, 1999] L-plastin (LP-P) Epithelial-derived tumours [Chung et al, 1999] α-lactalbumin (ALA), Breast midkine (MK) Pancreatic [Yoshida et al, 2002] cyclooxygenase-2 (COX-2) Gastrointestinal et al, 2001] probasin (ARR2PB) Prostate Rubinchik et al, 2001] tyrosinase promoter Melanoma [Park et al, 1999] hypoxic response elements (HRE) Not tissue-specific [Dachs et al, 2000;Ruan H, 2001] hTERT Not tissue-specific [Gu et al, 2000;Koga et al, 2000;Lin et al, 2002;Majumdar et al, 2001] flt-1, flk1/KDR, E-selectin, endoglin, ICAM-2, preproendothelin 1 (PPE-1) [Southgate et al, 2000] osteocalcin 2 Osteosarcoma [Barnett et al, 2002] ABBREVIATIONS: PSA/PMSA, prostate-specific membrane antigen; hTERT, human telomerase reverse transcr…”

Section: Promoters For Cancer Gene Therapymentioning

confidence: 99%

Promoters and Control Elements: Designing Expression Cassettes for Gene Therapy

Papadakis

Nicklin²,

Baker³

et al. 2004

CGT

146

121

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It has become apparent that the clinical success anticipated in the field of gene therapy has been limited by progress in several of the fundamental areas of genetics, molecular and cellular biology relevant to its application. Whilst a great deal of effort has been made in the evaluation of transgenes, it is only more recently with the advance of vector systems that attention has begun to be focused upon the means and control of transgene expression. Until recently, the majority of constructs have employed ubiquitous viral promoters to drive expression from simple gene expression cassettes using viral promoters and lacking introns, 3' untranslated regions (UTRs), locus control regions (LCR's), matrix attachment regions (MAR's) and other such genetic components. It has consequently emerged that these elements may have a key role in determining the levels and longevity of gene expression attainable in vivo, irrespective of the vector system utilised. The majority of gene therapy applications would also benefit from the specific optimisation of 'tailormade' expression cassettes to optimise their therapeutic efficacy. In conjunction with modification of vector tropism and strategies to limit their immunogenicity, this should create vectors suitable for the clinical application of gene therapy. This review aims to highlight some of the principle considerations of gene expression in vivo, and the means by which it may most effectively be achieved, whether this is via the minimal modification of an existing eukaryotic promoter or by the more extensive design of a novel promoter and associated elements.

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Section: Promoters For Cancer Gene Therapymentioning

confidence: 99%

Promoters and Control Elements: Designing Expression Cassettes for Gene Therapy

Papadakis

Nicklin²,

Baker³

et al. 2004

CGT

146

121

View full text Add to dashboard Cite

show abstract

“…Introduction of the respective reporter genes into HCC cell lines revealed that transcriptional activity of the 2.3-or 0.6-kb MK fragment was greater than that of the SV40 or the AFP promoter (Po0.001, Figure 2). Since HuH-7 and PLC/PRF/5 cells are AFPhigh and AFP-intermediate producers, respectively (Niwa et al, 1996;Ishikawa et al, 1999), the transcriptional activity of the AFP promoter was greater in HuH-7 than in PLC/PRF/5 cells. Addition of AFP enhancer augmented the AFP promoter-mediated transcriptional activation particularly in HuH-7 cells (Po0.001).…”

Section: Transcriptional Activity Of Mk and Afp Promotermentioning

confidence: 95%

“…Linkage of 0.2-kb AFP promoter and 0.9-kb AFP distal enhancer gave the maximal transcription of a fused reporter gene (Nakabayashi et al, 1991). We thereby examined the transcriptional activity of four kinds of reporter constructs (MK2.3-luc, MK0.6-luc, AFP0.2-luc and AFPEn0.2-luc) in AFP-producing (HuH-7 and PLC/PRF/5) and -nonproducing (HLE and HLF) HCC cell lines (Niwa et al, 1996;Ishikawa et al, 1999), and in non-HCC cell lines (MCF-7 and AsPC-1), which were positive for MK expression (Miyauchi et al, 2001). Introduction of the respective reporter genes into HCC cell lines revealed that transcriptional activity of the 2.3-or 0.6-kb MK fragment was greater than that of the SV40 or the AFP promoter (Po0.001, Figure 2).…”

Section: Transcriptional Activity Of Mk and Afp Promotermentioning

confidence: 99%

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

Tomizawa

Wada

et al. 2003

Br J Cancer

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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 a-fetoprotein promoter We examined the expression of the midkine (MK) and a-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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“…For this reason, several enhancers have been inserted into the upstream of the promoter in order to upgrade its activity [32][33][34][35] . In our study, the original enhancer in pshuttle was reserved, which might contribute to the satisfactory transcription of the downstream gene using the 0.3 kb promoter.…”

Section: Discussionmentioning

confidence: 99%

Construction of a targeting Adenoviral vector carrying AFP promoter for expressing EGFP gene in AFP producing hepatocarcinoma cell

Shi¹,

Gong²,

Liu³

et al. 2004

WJG

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AIM:To construct a recombinant adenoviral vector carrying AFP promoter and EGFP gene for specific expression of EGFP gene in AFP producing hepatocellular carcinoma (HCC) HepG2 cells. METHODS:Based on the Adeno-X TM expression system, the human immediate early cytomegalovirus promoter (P CMV IE ) was removed from the plasmid, pshuttle, and replaced by a 0.3 kb α-fetoprotein (AFP) promoter that was synthesized by polymerase chain reaction (PCR). The enhanced green fluorescent protein (EGFP) gene was inserted into the multiclone site (MCS), and then the recombinant adenovirus vector carrying the 0.3 kb AFP promoter and EGFP gene was constructed. Cells of a normal liver cell line (LO2), a hepatocarcinoma cell line (HepG2) and a cervical cancer cell line (HeLa) were transfected with the adenovirus. Northern blot and fluorescence microscopy were used to detect the expression of the EGFP gene at mRNA or protein level in three different cell lines. RESULTS:The 0.3 kb AFP promoter was synthesized through PCR from the human genome. The AFP promoter and EGFP gene were directly inserted into the plasmid pshuttle as confirmed by restriction digestion and DNA sequencing. Northern blot showed that EGFP gene was markedly transcribed in HepG2 cells, but only slightly in LO2 and HeLa cells. In addition, strong green fluorescence was observed in HepG2 cells under a fluorescence microscopy, but fluorescence was very weak LO2 and HeLa cells. CONCLUSION:Under control of the 0.3 kb human AFP promoter, the recombinant adenovirus vector carrying EGFP gene can be specially expressed in AFP-producing HepG2 cells. Therefore, this adenovirus system can be used as a novel, potent and specific tool for gene-targeting therapy for the AFP positive primary hepatocellular carcinoma.Shi YJ, Gong JP, Liu CA, Li XH, Mei Y, Mi C, Huo YY. Construction of a targeting Adenoviral vector carrying AFP promoter for expressing EGFP gene in AFP producing hepatocarcinoma cell.

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Utilization of variant-type of human α-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma

Cited by 38 publications

References 27 publications

Promoters and Control Elements: Designing Expression Cassettes for Gene Therapy

Promoters and Control Elements: Designing Expression Cassettes for Gene Therapy

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

Construction of a targeting Adenoviral vector carrying AFP promoter for expressing EGFP gene in AFP producing hepatocarcinoma cell

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