Cancer Res Treat.  2002 Aug;34(4):258-263.

Altered Retinoblastoma Protein Expression and Proliferative Activity in Urethane Induced Mouse Lung Tumorigenesis

• Chung JH
• Jang JJ
• Lee MJ
• Ham EK

Abstract

Lung cancer develops through a multistage process involving the accumulation of diverse genetic alterations. To gain an understanding of the roles played by tumor suppressor gene proteins and proliferating cell nuclear antigen (PCNA) in chemical carcinogen-induced mouse lung tumorigenesis, we examined the expression of retinoblastoma protein (Rb), p53, and PCNA in normal lung tissues and urethane-induced mouse lung tumors.
MATERIALS AND METHODS
ICR mice were given urethane by intra-peritoneal injection, and sacrificed at 5, 13, 21, 31, and 37 weeks following treatment. Sequential morphological changes and the immunohistochemical expression of Rb protein, p53, and (PCNA), during mouse lung tumorigenesis, were examined.
RESULTS
During the carcinogenesis, sequential histological changes from hyperplasia of type II pneumocytes, to adenomas, and ultimately to overt adenocarcinomas were noted. Intense nuclear staining of the Rb protein was observed in normal and hyperplastic alveolar epithelial cells and adenomas. In adenocarcinomas, the Rb protein expression was significantly diminished. The p53 mutant protein was not detected in any lesion. The PCNA labeling index increased along with the advance in the histological grade.
CONCLUSION
The above results indicate that mouse pulmonary adenocarcinomas develop through premalignant lesions, and down-regulation of the Rb protein expression may be implicated in the urethane-induced mouse lung tumorigenesis. In addition, the PCNA labeling index may reflect the malignant potential during the tumor progression.

Keyword

Lung neoplasm; Tumorigenesis; Urethane; Rb protein

MeSH Terms

Adenocarcinoma
Adenoma
Animals
Carcinogenesis*
Down-Regulation
Epithelial Cells
Genes, Tumor Suppressor
Hyperplasia
Lung Neoplasms
Lung*
Mice*
Mice, Inbred ICR
Mutant Proteins
Pneumocytes
Proliferating Cell Nuclear Antigen
Retinoblastoma Protein*
Retinoblastoma*
Urethane*
Mutant Proteins
Proliferating Cell Nuclear Antigen
Retinoblastoma Protein
Urethane