title: Downregulation of external death receptor genes FAS and DR5 in colorectal cancer samples positive for human papillomavirus infection.
abstract: OBJECTIVE
  Human papillomaviruses (HPV) have frequently been detected in colorectal cancer tumor samples, and may play a role in the pathogenesis of colorectal cancer. This study was designed to investigate the presence of DNA and RNA for the high-risk HPV genotypes 16 and 18 in samples of colorectal cancer tumors and adjacent normal tissues. We also investigated the expression of proapoptotic genes in HPV-positive colorectal tumors compared to normal tissue samples.
  
  
  METHODS
  Samples of tumoral and adjacent normal tissues were fresh-frozen, and HPV DNA was identified by nested and semiquantitative PCR. Real time PCR was used to quantitatively compare the expression of HPV-18 E6 and nine proapoptotic genes in HPV-positive tumors and samples of adjacent normal tissue.
  
  
  RESULTS
  HPV-16 DNA was found in 10.5% of the tumor samples, and HPV-18 DNA was found in 23.6% of the samples. Real time PCR results showed lower expression of the E6 gene in HPV-positive tumors than in adjacent normal tissue. The expression of two proapoptotic genes, FAS and DR5, was significantly lower in tumor samples than in adjacent normal tissues.
  
  
  CONCLUSIONS
  HPV infection, especially HPV-18, may play a role in colorectal cancer tumorigenesis by downregulating death receptor genes and interfering with the extrinsic pathway of apoptosis.
authors: Gastroenterology and Hepatology Department, Baqyiatallah Research Center for Gastroenterology and Liver Diseases, Tehran, Iran.
authors: Ashraf
authors: A
authors: Karbasi
authors: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Nasim
authors: N
authors: Borhani
authors: Medical Genetics Department, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Karim
authors: K
authors: Daliri
authors: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Biotechnology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Bahram
authors: B
authors: Kazemi
authors: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Biotechnology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: m.manoochehri@shmu.ac.ir.
authors: Mehdi
authors: M
authors: Manoochehri
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000821:virology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; C491901:FAS protein, human; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D019014:fas Receptor
keywords: Apoptosis; Colorectal cancer; Human papillomavirus