title: Expression and alteration of ras and p53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  The ras oncogene and the p53 tumor suppressor gene play important roles in the carcinogenic process of lung carcinoma. The authors evaluated whether alterations of the ras and p53 proteins may contribute to the development of lung carcinoma in patients with idiopathic pulmonary fibrosis (IPF) and whether such alterations may explain the high incidence of lung carcinoma among patients with IPF.
  
  
  METHODS
  Lung tissues were obtained from 35 patients who had IPF without complications of lung carcinoma and from 36 patients who had IPF with complications of lung carcinoma. Altered expression of ras and p53 proteins was evaluated by immunohistochemistry, and mutations of both genes were evaluated by polymerase chain reaction-single strand conformation polymorphism and sequencing analyses.
  
  
  RESULTS
  The frequency of expression of ras protein in type II alveolar pneumocytes was significantly greater in lung tissues from patients with IPF who had lung carcinoma compared with lung tissues from patients with IPF who did not have lung carcinoma (75% vs. 40%, respectively; P < 0.01). K-ras point mutation in codon 12 (GGT to GTT transversion) was detected in lung tissue with interstitial pneumonia, in which ras protein was overexpressed in type II alveolar pneumocytes obtained from 2 of 41 patients with IPF complicated by lung carcinoma, causing amino acid substitution (Gly to Val) in both patients. A p53 mutation was detected in three of six lung tissue samples from patients who had IPF lung with positive p53 immunoreactivity, and multiple mutations were detected in two samples.
  
  
  CONCLUSIONS
  Expression of ras protein in type II alveolar pneumocytes and mutation in the codon 12 of K-ras gene in lung tissue may contribute to the induction of lung carcinoma in patients with IPF. Furthermore, the presence of multiple mutations in the p53 gene may explain the high incidence lung carcinoma in patients with IPF.
authors.affiliation: First Department of Medicine, School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan. toruchan@med.hokudai.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Munakata
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohtsuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nisihara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nasuhara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamachi-Satoh
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Homma
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D016475:3T3 Cells; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins