Involvement of STAT3, NF-κB and associated downstream molecules before and after the onset of urethane induced lung tumors in mouse.

Here we have shown the alteration of transcription factors STAT3, NF-κB and downstream associated molecules much before the appearance of lung tumor and their response to antitumor agent, inositol hexaphosphate. Histological examination revealed the pathophysiology of the lung tissues and the onset or progression of tumor from 4 or 9 to 24 weeks in terms of tumor volume and the number. Over expression of NF-κB (p50/Rel A), COX-2, STAT3, pSTAT3 (Tyr 705), IL-6 and cyclin D1 also progressed from the time of no tumor to the time of tumor appearance and was reduced in mice drinking 2%IP6. We suggest that the alterations of STAT3, NF-κB and downstream associated molecules are critical in the development of lung tumors and can be exploited as possible mechanisms after the exposure. Status of these altered genes before the tumor development suggests their possible use as targets for the tumor control in the predisposed conditions.