Tuberc Respir Dis.  2007 Sep;63(3):251-260. 10.4046/trd.2007.63.3.251.

Expression of Caspase 3, Survivin, and p53 Protein in Urethane Induced Mouse Lung Carcinogenesis

• Shin JW
• Lee SH
• Park ES

• KMID: 1518416
• DOI: http://doi.org/10.4046/trd.2007.63.3.251

Abstract

PURPOSE: An imbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis. Capase 3, survivin and p53 have been identified as important members of the apoptotic related proteins. This study evaluated the proliferating cell nuclear antigen(PCNA), apoptosis, apoptotic related protein such as capase 3, survivin and p53 using urethane-induced mouse lung carcinogenesis, which provides reproducible steps from hyperplasia to adenocarcinoma.
METHODS
Urethane was administered to the ICR mice through an intra-peritoneal injection, The mice were sacrificed at 5, 15, and 25 weeks after urethane intervention. The sequential morphological changes and immunohistochemical expression of PCNA, apoptosis, capase 3, survivin, and p53 were examined during mouse lung carcinogenesis.
RESULTS
During carcinogenesis, the sequential histological changes were observed from hyperplasia of type II pneumocytes, to anadenoma, and ultimately to an overt adenocarcinoma. The PCNA Labeling index (LI) was 9.6% in hyperplasia, 23.2% in adenoma, and 55.7% in adenocarcinoma, respectively. The apoptotic LI was 0.24% in hyperplasia, 1.25% in adenoma, and 5.27% in adenocarcinoma. A good correlation was observed between the PCNA LI and apoptotic LI. The expression of caspase 3 was remarkable- i.e., 46.7% in adenocarcinoma, in contrast to 15% in hyperplasia and 16% in adenoma. Survivin was detected weakly in the alveolar hyperplasia and showed an increasing expressional pattern in adenoma and adenocarcinoma. p53 expression was detected only in the adenocarcinoma lesions with an expression rate of 13.3%. The level of caspase 3 expression correlated with the increase in the apoptotic index. The positive expression of caspase 3 was associated with an increased apoptotic index.
CONCLUSIONS
These results suggest that the PCNA LI and apoptotic LI might be useful markers for evaluating the risk of a malignant transformation. In addition, caspase, survivin and p53 might play a role in the early and late steges of urethane-induced mouse lung carcinogenesis.

Keyword

Survivin; caspase-3; p53; Lung cancer; Lung carcinogenesis; PCNA; Apoptosis

MeSH Terms

Adenocarcinoma
Adenoma
Animals
Apoptosis
Carcinogenesis*
Caspase 3*
Cell Proliferation
Hyperplasia
Lung Neoplasms
Lung*
Mice*
Mice, Inbred ICR
Pneumocytes
Proliferating Cell Nuclear Antigen
Urethane*
Caspase 3
Proliferating Cell Nuclear Antigen
Urethane

Figure

• 

  Figure 1 A. Gross finding of urethane-induced lungs, which shows multiple masses. B, C. Sequential change in urethane-induced lung lesions, showing adenoma (Figure 1B) and infiltrating adenocarcinoma (Figure 1C)(Hematoxylline & Eosin Stain, ×200). D. Immunohistochemical reactivity for PCNA in adenoma (×200). E. TUNNEL stain shows occasional nuclear staining in adenocarcinoma of lung (×200). F, G, H. Immunohistochemical reactivity for capase 3 (Figure 1F), p53 (Figure 1G) and survivin protein (Figure 1H) showing positive cytoplasmic staining (×200).

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