Pathobiological Implications of MUC4 in Non–Small-Cell Lung Cancer
| Autor: | Poonam Sharma, Moorthy P. Ponnusamy, Sonny L. Johansson, Sukwinder Kaur, Srustidhar Das, Surinder K. Batra, Lynette M. Smith, Prabin D. Majhi, Imayavaramban Lakshmanan, Fang Yu, Maneesh Jain, Cleo E. Rolle, Apar Kishor Ganti, William W. West, George B. Carey, Su Tomohiro Shimizu |
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| Rok vydání: | 2013 |
| Předmět: |
p53
Oncology Pulmonary and Respiratory Medicine medicine.medical_specialty Lung Neoplasms Blotting Western Apoptosis Biology Adenocarcinoma Real-Time Polymerase Chain Reaction Metastasis Immunoenzyme Techniques Invasion Cell Movement Internal medicine Carcinoma Non-Small-Cell Lung medicine Carcinoma Biomarkers Tumor Humans RNA Messenger Lung cancer Protein kinase B Survival rate Cell Proliferation Neoplasm Staging Mucin-4 Cell growth Reverse Transcriptase Polymerase Chain Reaction Cell Cycle EMT Motility Cell cycle medicine.disease Prognosis Small Cell Lung Carcinoma Survival Rate Real-time polymerase chain reaction MUC4 Tissue Array Analysis Carcinoma Squamous Cell sense organs |
| Zdroj: | Journal of Thoracic Oncology. 8(4):398-407 |
| ISSN: | 1556-0864 |
| DOI: | 10.1097/jto.0b013e3182829e06 |
| Popis: | Introduction Altered expression of MUC4 plays an oncogenic role in various cancers, including pancreatic, ovarian, and breast. This study evaluates the expression and role of MUC4 in non–small-cell lung cancer (NSCLC). Methods We used a paired system of MUC4-expressing (H292) and MUC4-nonexpressing (A549) NSCLC cell lines to analyze MUC4-dependent changes in growth rate, migration, and invasion using these sublines. We also evaluated the alterations of several tumor suppressor, proliferation, and metastasis markers with altered MUC4 expression. Furthermore, the association of MUC4 expression (by immunohistochemistry) in lung cancer samples with patient survival was evaluated. Results MUC4-expressing lung cancer cells demonstrated a less proliferative and metastatic phenotype. Up-regulation of p53 in MUC4-expressing lung cancer cells led to the accumulation of cells at the G2/M phase of cell cycle progression. MUC4 expression attenuated Akt activation and decreased the expression of Cyclins D1 and E, but increased the expression of p21 and p27. MUC4 expression abrogated cancer cell migration and invasion by altering N- & E-cadherin expression and FAK phosphorylation. A decrease in MUC4 expression was observed with increasing tumor stage (mean composite score: stage I, 2.4; stage II, 1.8; stage III, 1.4; and metastatic, 1.2; p = 0.0093). Maximal MUC4 expression was associated with a better overall survival ( p = 0.042). Conclusion MUC4 plays a tumor-suppressor role in NSCLC by altering p53 expression in NSCLC. Decrease in MUC4 expression in advanced tumor stages also seems to confirm the novel protective function of MUC4 in NSCLC. |
| Databáze: | OpenAIRE |
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