Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by α-lactalbumin promoter

Li, Xiong; Zhang, Jie; Gao, Huanling; Vieth, Edyta; Bae, Kyung Hee; Zhang, Yan Ping; Lee, Sang Jin; Raikwar, Sudhanshu P.; Gardner, Thomas A.; Hutchins, Gary D.; VanderPutten, Dale; Kao, Chinghai; Jeng, Meei-Huey

doi:10.1158/1535-7163.mct-05-0167

Cited by 19 publications

(11 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transcriptional targeting takes advantage of the fact that promoters of the genes which are exclusively expressed in cancer cells, could be used for specific expression of lethal genes in cancer cells. 37 Similar work, using Erb-B2, 38 PPAR-c1, 39 a-lactalbomin, 40 mammaglobin, 41 and L-plastin promoters 42 have been reported for specific expression of lethal gene in breast cancer cells. Erb-B2 promoter was used for specific expression of HSV-tk transgene in breast cancer cells, 38 but over-expression also occurs in other malignancies such as ovarian cancer and stomach cancer.…”

Section: Discussionsupporting

confidence: 60%

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting

Farokhimanesh

Rahbarizadeh

Rasaee

et al. 2009

Biotechnology Progress

View full text Add to dashboard Cite

Developing cancer gene therapy constructs based on transcriptional targeting of genes to cancer cells is a new and promising modality for treatment of cancer. Introducing truncated Bid (tBid), a recently known member of the Bcl-2 family, eradicates cancer cells efficiently. For transcriptional targeting of tBid, two dual-specificity promoters, combining cancer specific core promoters and response modules, were designed. These two core promoter modules contained cancer specific promoters of MUC1 and Survivin genes accompanied by hypoxia-responsive elements and estrogen responsive elements (microenvironment condition of breast cancer cells) which were employed to achieve a higher and more specific level of tBid expression in breast cancer cells. Correlation of the level of tBid expression in normal and cancer cell lines with promoter activity was measured by RT-PCR after treatment with hypoxia and estrogen. The level of tBid expression under control of new hybrid promoters was compared with its expression under control of cytomegalovirus (CMV) promoter as a control. Our data revealed that the level of tBid expression in breast cancer cells were nearly 11 times more than normal cells because of the cancer specific promoters, although tBid expression under control of CMV promoter was almost the same in normal and cancer cell lines. Increased apoptosis was detected in the transfected breast cancer cell lines by the Caspase-3 activity assay. The application of these promoters may prove to have the advantage of tumor selective gene therapy in breast cancer cells and low-potential toxicity for normal tissues.

show abstract

Section: Discussionsupporting

confidence: 60%

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting

Farokhimanesh

Rahbarizadeh

Rasaee

et al. 2009

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…Adenovirus-mediated gene therapy has been tested broadly in clinical trials, and tumor/tissue-restricted replicative adenovirus showed significant advantages over replication-deficient adenovirus (14,28,29). However, the single administration of PRRA ultimately results in failure due to inefficient viral distribution in tumor masses (12,14).…”

Section: Discussionmentioning

confidence: 99%

Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy

Xiong

Liu

Lee

et al. 2008

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Our previous studies coadministering a replication-deficient adenovirus expressing endostatin and angiostatin fusion gene (EndoAngio) and a prostate-restricted, replicationcompetent adenovirus (PRRA) showed dramatic antitumor efficacy. This study integrated EndoAngio with an improved PRRA vector to make a single antiangiogenic PRRA, thereby exerting a similarly dramatic antitumor effect with feasibility for future clinical trials. Experimental Design: We developed an antiangiogenic PRRA with structural improvements. The antitumor efficacy of EndoAngio-PRRA was evaluated in prostate-specific antigen/ prostate-specific membrane antigen (PSA/PSMA)-positive, androgen-independent CWR22rv tumor models. The tumor vasculature and cell morphology were observed by dual-photon microscopy. The antiangiogenic effect of EndoAngio delivered by PRRA and the killing activity of EndoAngio-PRRA were evaluated in vitro. Virus-inactivated conditioned media from virusinfected PSA/PSMA-positive cells were tested for apoptosis induction in prostate cancer cells. Results: Our novel EndoAngio-PRRA is a strong antiangiogenic and antitumor agent. Nine of 10 CWR22rv tumors treated by EndoAngio-PRRA completely regressed, with 1tumor remaining in a dormant status for 26 weeks after treatment. Dual-photon microscopy revealed that EndoAngio-PRRA not only inhibited the development of tumor vasculature but also induced apoptosis in tumor cells. Subsequent in vitro study indicated that EndoAngio-PRRA exhibited stronger tumor-specific killing activity than enhanced green fluorescent protein-PRRA, which expresses enhanced green fluorescent protein instead of EndoAngio. Virus-inactivated conditioned medium from EndoAngio-PRRA^infected PSA/PSMA-positive cells induced apoptosis in C4-2 and CWR22rv cells. Conclusions: EndoAngio-PRRA uniquely combines three distinct antitumor effects to eliminate androgen-independent prostate cancer: antiangiogenesis, viral oncolysis, and apoptosis. This novel antiangiogenic PRRA represents a powerful agent feasible for future clinical trials for prostate cancer therapy.

show abstract

“…Similarly, the promoter region of breast-specific α lacta albumin (ALA) has been employed to generate two CRAds: AdALAE1a with E1a under the control of ALA promoter and AdE1aALAE1b with both E1a and E1b genes driven by α lacta albumin promoter, respectively. AdE1aALAE1b inhibited tumor growth of hormoneindependent breast tumors in a mouse xenograft model [87].…”

Section: Albumin Promotermentioning

confidence: 97%

Oncolytic Viruses Driven by Tumor-Specific Promoters

Hardcastle¹,

Kurozumi²,

Chiocca³

et al. 2007

CCDT

View full text Add to dashboard Cite

Oncolytic viruses can selectively replicate in and lead to tumor cell lysis with minimal infection/replication potential in adjoining non-neoplastic tissue. Because of paramount safety concerns, first-generation oncolytic viruses were designed to be significantly attenuated in their lytic potential. Results from recent clinical trials have revealed the safety of this approach, but have underscored the urgency for design and testing of more tumor-selective and -potent viruses to realize the full therapeutic potential of this revolutionary treatment modality. With the discovery of various molecular/genetic changes associated with neoplasia, tumor-specific transcriptional targeting of viral virulence is being tapped to generate tumor- and tissue-specific variants. This review will focus on the various strategies exploited to generate viruses whose virulence is governed by tumor-specific transcriptional events.

show abstract

Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by α-lactalbumin promoter

Cited by 19 publications

References 47 publications

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting

Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy

Oncolytic Viruses Driven by Tumor-Specific Promoters

Contact Info

Product

Resources

About