Expression and significance of transforming growth factor-β receptor type II and DPC4/Smad4 in non-small cell lung cancer

Chen,Hong; Wang,Jing‑Wei; Liu,Li‑Xin; Yan,Ji‑Dong; Ren,Shu‑Hua; Li,Yan; Lu,Zheng

doi:10.3892/etm.2014.2065

Expression and significance of transforming growth factor-β receptor type II and DPC4/Smad4 in non-small cell lung cancer

Authors:
- Hong Chen
- Jing‑Wei Wang
- Li‑Xin Liu
- Ji‑Dong Yan
- Shu‑Hua Ren
- Yan Li
- Zheng Lu
View Affiliations

Affiliations: Department of Radiotherapy and Chemotherapy, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Department of Thoracic Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China
Published online on: November 12, 2014 https://doi.org/10.3892/etm.2014.2065
Pages: 227-231

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the expression levels of transforming growth factor‑β (TGF‑β) receptor type II (TβRII) and DPC4/Smad4 in the TGF‑β signaling pathway and the importance of these expression levels in non‑small cell lung cancer (NSCLC). The mRNA and protein expression levels of TβRII and DPC4/Smad4 were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively, in NSCLC and control nonlesional lung tissues of 60 patients. The protein expression levels of DPC4/Smad4 were detected by immunohistochemistry in paraffin‑embedded samples of NSCLC. In addition, the correlations among the expression levels of TβRII and DPC4/Smad4 and their association with the clinical and pathological features of NSCLC were analyzed. The expression levels of TβRII and DPC4/Smad4 in NSCLC tissues were significantly lower when compared with the control nonlesional lung tissues (P<0.05). In addition, the expression of TβRII and DPC4/Smad4 in poorly‑differentiated NSCLC tissues was significantly lower compared with moderately‑ or well‑differentiated NSCLC tissues (P<0.05). The expression levels of TβRII and DPC4/Smad4 were significantly lower in NSCLC tissues with metastatic lymph nodes compared with tissue without metastatic lymph nodes (P<0.05). Thus, the expression levels were demonstrated to significantly correlate with the clinical and pathological stages, and subsequently were shown to be associated with the occurrence and progression of NSCLC. In conclusion, TβRII and DPC4/Smad4 may play an important role in the tumorigenesis, differentiation and progression of NSCLC via the TGF‑β signaling pathway.

View Figures

View References

1	Ginsberg RJ, Vokes EE and Raben A: Non-small cell lung cancer. Cancer Principles and Practice of Oncology. DeVita VT Jr, Hellman S and Rosenberg SA: 5th edition. Lippincott-Raven Publishers; Philadelphia, PA: pp. 858–911. 1997
2	Wrana JL, Attisano L, Weiser R, Ventura F and Massagué J: Mechanism of activation of the TGF-beta receptor. Nature. 370:341–347. 1994. View Article : Google Scholar : PubMed/NCBI
3	Moustakas A, Souchelnytskyi S and Heldin CH: Smad regulation in TGF-beta signal transduction. J Cell Sci. 114:4359–4369. 2001.
4	Hahn SA, Schutte M, Hoque AT, et al: DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 271:350–353. 1996. View Article : Google Scholar : PubMed/NCBI
5	Dumont N, Bakin AV and Arteaga CL: Autocrine transforming growth factor-beta signaling mediates Smad-independent motility in human cancer cells. J Biol Chem. 278:3275–3285. 2003. View Article : Google Scholar
6	Takanami I, Tanaka F, Hashizume T and Kodaira S: Roles of the transforming growth factor beta 1 and its type I and II receptors in the development of a pulmonary adenocarcinoma: results of an immunohistochemical study. J Surg Oncol. 64:262–267. 1997. View Article : Google Scholar : PubMed/NCBI
7	UICC. International Union Against Cancer. TNM Classification of Malignant Tumours. Sixth edition. Wiley-Liss; New York, NY: 2002
8	Ke Z, Zhang X, Ma L and Wang L: Expression of DPC4/Smad4 in non-small-cell lung carcinoma and its relationship with angiogenesis. Neoplasma. 55:323–329. 2008.PubMed/NCBI
9	Knaus PI, Lindemann D, DeCoteau JF, et al: A dominant inhibitory mutant of the type II transforming growth factor beta receptor in the malignant progression of a cutaneous T-cell lymphoma. Mol Cell Biol. 16:3480–3489. 1996.PubMed/NCBI
10	Kim IY, Ahn HJ, Lang S, et al: Loss of expression of transforming growth factor-beta receptors is associated with poor prognosis in prostate cancer patients. Clin Cancer Res. 4:1625–1630. 1998.PubMed/NCBI
11	Tokunaga H, Lee DH, Kim IY, Wheeler TM and Lerner SP: Decreased expression of transforming growth factor beta receptor type I is associated with poor prognosis in bladder transitional cell carcinoma patients. Clin Cancer Res. 5:2520–2525. 1999.PubMed/NCBI
12	Park K, Kim SJ, Bang YJ, Park JG, Kim NK, Roberts AB and Sporn MB: Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. Proc Natl Acad Sci USA. 91:8772–8776. 1994. View Article : Google Scholar : PubMed/NCBI
13	Kim WS, Park C, Jung YS, et al: Reduced transforming growth factor-beta type II receptor (TGF-beta RII) expression in adenocarcinoma of the lung. Anticancer Res. 19:301–306. 1999.PubMed/NCBI
14	Kang Y, Prentice MA, Mariano JM, et al: Transforming growth factor-beta 1 and its receptors in human lung cancer and mouse lung carcinogenesis. Exp Lung Res. 26:685–707. 2000. View Article : Google Scholar
15	Wilentz RE, Iacobuzio-Donahue CA, Argani P, et al: Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res. 60:2002–2006. 2000.PubMed/NCBI
16	Wilentz RE, Su GH, Dai JL, et al: Immunohistochemical labeling for dpc4 mirrors genetic status in pancreatic adenocarcinomas: a new marker of DPC4 inactivation. Am J Pathol. 156:37–43. 2000. View Article : Google Scholar : PubMed/NCBI
17	de Caestecker MP, Piek E and Roberts AB: Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst. 92:1388–1402. 2000. View Article : Google Scholar : PubMed/NCBI
18	Garrigue-Antar L, Muñoz-Antonia T, Antonia SJ, Gesmonde J, Vellucci VF and Reiss M: Missense mutations of the transforming growth factor beta type II receptor in human head and neck squamous carcinoma cells. Cancer Res. 55:3982–3987. 1995.PubMed/NCBI
19	Markowitz S, Wang J, Myeroff L, et al: Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science. 268:1336–1338. 1995. View Article : Google Scholar : PubMed/NCBI
20	Derynck R, Akhurst RJ and Balmain A: TGF-beta signalling in tumor suppression and cancer progression. Nat Genet. 29:117–129. 2001. View Article : Google Scholar : PubMed/NCBI