Deleted in pancreatic carcinoma locus 4/Smad4 participates in the regulation of apoptosis by affecting the Bcl-2/Bax balance in non–small cell lung cancer

Ke, Zunfu; Zhang, Xiaowen; Ma, Lanlan; Wang, Liantang

doi:10.1016/j.humpath.2008.03.006

« Previous Next »Human Pathology
Volume 39, Issue 10 , Pages 1438-1445, October 2008

Deleted in pancreatic carcinoma locus 4/Smad4 participates in the regulation of apoptosis by affecting the Bcl-2/Bax balance in non–small cell lung cancer☆

Zunfu Ke, PhD
- Department of Pathology, Medical School of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, PR China
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, PR China
Xiaowen Zhang, PhD
- Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Guangzhou Medical College, Guangzhou 510080, PR China
Lanlan Ma, PhD
- Department of Pathology, Medical School of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, PR China
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, PR China
Liantang Wang, PhD
- Department of Pathology, Medical School of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, PR China
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, PR China
- Corresponding author. Department of Pathology, Medical School of Sun Yat-Sen University, Guangzhou 510080, PR China.

Received 28 November 2007; received in revised form 3 March 2008; accepted 21 March 2008. published online 14 July 2008.

Summary

Deleted in pancreatic carcinoma locus 4 influences tumorigenesis and tumor progression by various mechanisms, including apoptosis. The aim of this study is to determine whether deleted in pancreatic carcinoma locus 4 participates in apoptosis in lung cancer and clarify its relationship with clinical parameters of non–small cell lung cancer. Immunohistochemical results revealed that the positive rate of deleted in pancreatic carcinoma locus 4 in normal tracheal-bronchial epithelium (89.5%, 17/19) was much higher than that in tumor tissues (63.5%, 33/52) (P < .05) and closely correlated with lymph node metastasis (P < .001). These results were further confirmed by Western blot analysis. Furthermore, deleted in pancreatic carcinoma locus 4 overexpression was inversely associated with Bcl-2 immunostaining (P < .01), and the apoptosis index in deleted in pancreatic carcinoma locus 4-positive carcinomas (8.65 ± 1.46) was much higher than that in deleted in pancreatic carcinoma locus 4–negative carcinomas (2.12 ± 0.04) (P < .05). The results of deleted in pancreatic carcinoma locus 4 small interfering RNA in A549 cells also showed that deleted in pancreatic carcinoma locus 4 could inhibit cell proliferation, decrease Bcl-2 mRNA and protein expression, and increase Bax messenger RNA and protein expression. These findings indicated that Deleted in pancreatic carcinoma locus 4 might be an important biomarker for malignant transformation and be involved in inducing apoptosis by modulating Bcl-2/Bax balance.

Keywords: DPC4, Lung cancer, Bcl-2, Bax, Apoptosis