Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of HER-2/neu has been demonstrated in human ovarian cancer and correlated with poor prognosis. We previously found that the adenovirus type 5 early region 1A (E1A) gene product can repress overexpression and suppress the tumorigenic potential of the HER-2/neu-overexpressing cancer cells. To develop an efficient HER-2/neu-targeting gene therapy with E1A, a replication-deficient adenovirus containing the E1A gene, Ad.E1A(+), was used to transduce the HER-2/neu-overexpressing human ovarian cancer cell line SK-OV3.ip1. Tumor cell growth in vitro and colony formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction. To test therapeutic efficacy in vivo, tumor-bearing mice were established by i.p. injection with ovarian cancer cells and treated by i.p. injection of 10(8) PFU viral solution containing either replication-deficient Ad.E1A(+); control virus Ad.E1A(-) which is the same adenovirus as Ad.E1A(+) except for E1A deletion, or just PBS. Ad.E1A(+) significantly prolonged survival in treated mice for 1 year (80%) whereas in control groups, all mice died of cancer within 4.5 months. Immunohistochemistry analysis indicated that Ad.E1A protein was expressed in tumor tissue and expression of HER-2/neu p185 protein was suppressed in vivo. As a control, another ovarian cancer cell line 2774, in which HER-2/neu is expressed at a basal level, was also inoculated i.p. following the same therapeutic procedure. Ad.E1A(+) could not prolong survival of 2774 cells, indicating that Ad.E1A(+) specifically targeted HER-2/neu-overexpressing tumor cells and functioned as an antitumor agent.
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PMID:HER-2/neu-targeting cancer therapy via adenovirus-mediated E1A delivery in an animal model. 776 Oct 95

The HER-2/neu proto-oncogene is frequently amplified or overexpressed in human breast and ovarian cancers, and is significantly correlated with shorter survival. We have previously reported that the adenovirus type 5 early region 1A (E1A) gene product can repress HER-2/neu overexpression by repressing HER-2/neu promoter activity, and suppress the tumorigenic potential of HER-2/neu-overexpressing ovarian cancer cells. To examine E1A tumor suppressor function in breast cancer, we transduced E1A in vitro by adenovirus into both HER-2/neu-overexpressing and low expressing human breast cancer cell lines. In HER-2/neu-overexpressing cells, E1A greatly inhibited tumor cell growth in vitro. However, in HER-2/neu low expressing cancer cell lines, E1A had no significant effect on cell growth in culture medium. To test the therapeutic efficacy of E1A, we used both adenovirus-mediated and cationic liposome-mediated E1A gene delivery systems in an orthotopic breast cancer animal model. An advanced breast cancer model was established by inoculation of HER-2/neu-overexpressing human breast cancer cells in mammary fat pad and treated by local injections of either replication-deficient adenovirus expressing E1A, Ad.E1A(+) or a liposome-E1A DNA complex. As controls, mice bearing tumors were also treated with Ad.E1A(-) which is virtually the same adenovirus as Ad.E1A(+) except that E1A is deleted, a liposome-E1A frame-shift mutant DNA complex, or just PBS. In mice bearing a HER-2/neu-overexpressing breast cancer cell line, E1A delivered either by adenovirus or liposome significantly inhibited tumor growth and prolonged mouse survival compared with the controls. In fact, 60-80% of E1A-treated mice lived longer than 2 years versus only 0-20% of control mice (P<0.05). Western blot analysis showed that E1A protein was expressed in tumor tissue and immunohistochemical analysis showed that HER-2/neu p185 protein expression was suppressed. Taken together, our results indicated that both adenovirus and cationic liposome delivery systems were effective in transfering E1A gene for tumor suppression in a HER-2/neu-overexpressing breast cancer model.
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PMID:The tumor suppression activity of E1A in HER-2/neu-overexpressing breast cancer. 905 54

The aim of this study was to investigate therapeutic efficacy of adenovirus-mediated E1a gene therapy for ovarian cancer in vitro and in vivo. Recombinant replication-deficient adenoviral vectors were prepared by superinfection of 293 cells, and then purified. The efficacy of the adenovirus vector system to infect ovarian cells was tested using different multiplicity of infection (MOI) and different times (1-4) of Ad.RSVlacZ. SKOV-3 cells (10(3) per well) were infected once with 2 x 10(4) adenovirus. The cells were harvested and counted on different days for 7 days to generate the in vitro growth curve. Tumor-bearing mice were injected intraperitoneally with ovarian cancer cells and treated by intraperitoneal injection of 100 microl (2.5 x 10(8) PFU) viral solution containing either replication-deficient Ad.E1a(+); control virus Ad.E1a(-) which is the same adenovirus as Ad.E1a(+) except for E1a deletion, or just phosphate buffered solution. The transduction efficacy increased with higher MOI and reached a plateau at the 20:1 ratio. When Ad.E1a(+) was used to transduce the HER-2/neu overexpressing human ovarian cancer cell line SKOV-3, tumor cell growth in vitro was greatly inhibited by E1a transduction. Also, Ad.E1a+ greatly inhibited tumor growth of SKOV-3-bearing mice. Immunohistochemistry analysis indicated that Ad.E1a protein was expressed in tumor tissue and expression of HER-2/neu p185 protein was suppressed. Very strong beta-gal staining was detected in tumors, and beta-gal activity in small intestine, lung, heart, stomach, liver, and kidney was detected. No beta-gal activity was detected in the tumor and other organs in control mice injected with Ad.E1a(-) or PBS. Adenovirus-type 5 E1a gene can efficaciously inhibit HER-2/neu-overexpressing ovarian cancer, and this promising procedure could greatly benefit ovarian cancer patients with high expression of HER-2/neu.
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PMID:Adenovirus 5 E1a-mediated gene therapy for human ovarian cancer cells in vitro and in vivo. 1128 29