title: Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.
abstract: Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.
authors.affiliation: Department of Health Science, University of Jaén, Jaén 23071, Spain. arama@ujaen.es.|Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, Spain. arama@ujaen.es.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Rama
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, Spain. r_faraya@hotmail.com.|Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada 18071, Spain. r_faraya@hotmail.com.|Department of Human Anatomy and Embryology, School of Medicine, University of Granada, Granada 18012, Spain. r_faraya@hotmail.com.
authors.forename: Rosa
authors.initials: R
authors.lastname: Hernandez
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, Spain. gperazzoli@ugr.es.|Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada 18071, Spain. gperazzoli@ugr.es.
authors.forename: Gloria
authors.initials: G
authors.lastname: Perazzoli
authors.affiliation: Institute of Biotechnology and Department of Genetics, University of Granada, Granada 18071, Spain. mburgos@ugr.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Burgos
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, Spain. melguizo@ugr.es.|Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada 18071, Spain. melguizo@ugr.es.|Department of Human Anatomy and Embryology, School of Medicine, University of Granada, Granada 18012, Spain. melguizo@ugr.es.
authors.forename: Consolación
authors.initials: C
authors.lastname: Melguizo
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, Spain. mariaceliavelez@ugr.es.|Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada 18071, Spain. mariaceliavelez@ugr.es.|Department of Human Anatomy and Embryology, School of Medicine, University of Granada, Granada 18012, Spain. mariaceliavelez@ugr.es.
authors.forename: Celia
authors.initials: C
authors.lastname: Vélez
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, Spain. jcprados@ugr.es.|Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada 18071, Spain. jcprados@ugr.es.|Department of Human Anatomy and Embryology, School of Medicine, University of Granada, Granada 18012, Spain. jcprados@ugr.es.
authors.forename: Jose
authors.initials: J
authors.lastname: Prados
mesh_terms: D000818:Animals; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000628:therapy* / Q000821:virology; D015316:Genetic Therapy / Q000379:methods*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002272:Carcinoembryonic Antigen; D011994:Recombinant Proteins; D014764:Viral Proteins
keywords: E gene; carcinoma embryonic antigen; colorectal cancer; promoter tissue specific; suicide gene therapy