HDAC1 is indirectly involved in the epigenetic regulation of p38 MAPK that drive the lung cancer progression

Z.-Y. Dong, Y.-R. Zhou, L.-X. Wang

Department of Integrated Chinese and Western Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. LlewellynMngogi@yahoo.com

---

• Oncology

OBJECTIVE: p38 MAPK are a class of protein kinase that may induce or prevent apoptosis in different circumstance. Emerging researches show that it plays a vital role in tumor progression and therefore understanding its dual role in different stages of lung cancer are important to investigate. Also in this study, we planned to understand its upstream target proteins like HDAC1 and uPAR which are responsible for p38 MAPK activation in the pathway.

MATERIALS AND METHODS: We initially develop lung cancer mice model by exposing them to high nicotine content tobacco smoke. The pathological stages of initial and advanced lung cancer are observed and confirmed through histological sectioning. The expression of HDAC1, uPAR and p38 MAPK are observed and analyzed in different stages of lung cancer using immunohistochemistry and Western blotting.

RESULTS: After 4 and 6 months of regular exposure of high nicotine content smoke, the A/J strain mice develop initial and advanced stage of lung cancer. The initial stage cancer develops thick tissue layers with fibrosis whereas advanced stages of lung cancer show more proliferative cells. The expression of HDAC1 and uPAR shows the minimal expression pattern in control and initial stages of lung cancer, but its expression increased in advanced stage of cancer. In case of phospho-p38 MAPK, mild expression was observed almost in every individual cell in the initial stages of cancer, which implies its protective role in preventing advanced stage of cancer. But in advanced stage of lung cancer, we observed dysregulated overexpression of phospho-p38 MAPK.

CONCLUSIONS: The epigenetic regulation of uPAR by HDAC1 confirms its indirect role in regulating p38 MAPK as tumor progress.

Free PDF Download