title: Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.
abstract: The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs) are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4) and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR) and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs) and the potential development of colon cancer.
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Abdelhabib
authors.initials: A
authors.lastname: Semlali
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Amri
authors.affiliation: College of Medicine, Al Imam Muhammad Ibn Saud Islamic University (IMSIU), Riyadh, Kingdom of Saudi Arabia.
authors.forename: Arezki
authors.initials: A
authors.lastname: Azzi
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Omair
authors.initials: O
authors.lastname: Al Shahrani
authors.affiliation: College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Maha
authors.initials: M
authors.lastname: Arafah
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Kohailan
authors.affiliation: College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdulrahman M
authors.initials: AM
authors.lastname: Aljebreen
authors.affiliation: College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Othman
authors.initials: O
authors.lastname: Alharbi
authors.affiliation: Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia; Division of Gastroenterology, The McGill University Health Center, Montreal General Hospital, McGill University, Montreal, Canada.
authors.forename: Majid A
authors.initials: MA
authors.lastname: Almadi
authors.affiliation: College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nahla Ali
authors.initials: NA
authors.lastname: Azzam
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Narasimha Reddy
authors.initials: NR
authors.lastname: Parine
authors.affiliation: Groupe de Recherche en Écologie Buccale, Département de stomatologie, Faculté de Médecine Dentaire, Université Laval, Québec, Québec, Canada.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Rouabhia
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Alanazi
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D023083:beta-Defensins