Regulation of VIP gene expression in general. Human lung cancer cells in particular

Vasoactive intestinal peptide (VIP) is a neuropeptide of multiple functions affecting development and aging. In cancer, for example, VIP was found to function as an autocrine growth factor in nonsmall cell lung cancer (NSCLC) promotion. Furthermore, a VIP hybrid antagonist (neurotensin(6-11)-VIP(7-28)) was found to inhibit NSCLC growth. In the present study, the expression of VIP mRNA was studied using human lung cancer cells. RNA prepared from 19 cell lines was fractionated by 1% agarose gel electrophoresis followed by blotting onto nitrocellulose membranes and hybridization to a VIP-specific RNA probe. VIP mRNA was detected in about 50% of the cell lines tested with a greater abundance in NSCLC. Cultures of the NSCLC NCI-H727 cell line were treated with forskolin, an activator of cyclic AMP (cAMP), and separately with the tumor promoter phorbol 12-myristate 13-acetate (PMA). Northern blot hybridization analysis showed an increase in VIP mRNA levels after 4 h treatment with 50 microM forskolin. Incubation with PMA also showed a significant increase in the levels of VIP transcripts. Cultures were then incubated with PMA in the presence of actinomycin D, a transcription blocker. Results indicated that PMA treatment may induce both VIP mRNA synthesis as well as VIP mRNA stabilization, and suggested a 4-5 h half-life for the VIP mRNA in the absence of PMA. Thus, lung cancer tumor proliferation may be regulated, in part, at the level of VIP gene expression.