Expression of vascular endothelial growth factor and its receptors during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine in rats

Mol Carcinog. 1999 Apr;24(4):287-93.

Abstract

The expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), VEGFR-1/Flt-1 and VEGFR-2/Flk-1, was investigated by immunohistochemical and northern blot analysis during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Wistar rats. After BHP was given in the drinking water for 12 wk, the rats were maintained without further treatment until they were killed at 20-28 wk. Immunohistochemical studies revealed VEGF expression in almost all malignancies, the reaction being strongly positive in most adenocarcinomas (15 of 18; 83.3%) and squamous cell carcinomas (four of five; 80.0%), but less so in a total of 120 adenomas and 136 alveolar hyperplasias. In addition, VEGF mRNA and VEGFR mRNAs were found to be overexpressed in most adenocarcinomas and squamous cell carcinomas as well as in one to three of the five adenomas tested. The results indicated that VEGF and VEGFRs play important roles in the acquisition of malignant potential by preneoplastic lung lesions induced by BHP in rats. Moreover, overexpression of VEGF was related to upregulation of VEGFR-1/Flt-1 and VEGFR-2/Flk-1 expression in malignant and premalignant lung lesions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenoma / chemically induced
  • Adenoma / genetics
  • Adenoma / metabolism*
  • Animals
  • Blotting, Northern
  • Carcinogens / toxicity*
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Disease Progression
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, ras
  • Hyperplasia
  • Lung Diseases / chemically induced
  • Lung Diseases / genetics
  • Lung Diseases / metabolism*
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lymphokines / biosynthesis*
  • Lymphokines / genetics
  • Male
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neovascularization, Pathologic* / genetics
  • Nitrosamines / toxicity*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Growth Factor / biosynthesis*
  • Receptors, Growth Factor / genetics
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors

Substances

  • Carcinogens
  • Endothelial Growth Factors
  • Lymphokines
  • Neoplasm Proteins
  • Nitrosamines
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • diisopropanolnitrosamine
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1