ALTERNATIVE SPLICING OF THE NEUROFIBROMATOSIS-1 GENE CORRELATES WITH GROWTH-PATTERNS AND NEUROENDOCRINE PROPERTIES OF HUMAN SMALL-CELL LUNG-CARCINOMA CELLS

Two distinct transcripts, type I and type II, of the neurofibromatosis I (NFI) gene are generated by alternative splicing in the region corr esponding to the gene's GTPase-activating protein-related domain (GRD) . Relative expression levels of these 2 transcripts were previously co rrelated to neural differentiation. Since small-cell lung carcinoma (S CLC) often exhibits neuroendocrine properties, we analyzed the type-I to type-II mRNA ratio in 15 SCLC cell lines, using reverse transcripta se and polymerase chain reaction methods. The type-I mRNA was predomin ant in 10 cell lines; 8 of them grew as floating aggregates in culture and had high L-dopa decarboxylase (DDC) activity. The other 5 lines p redominantly expressed type-II mRNA, adhered to the culture substrate, and expressed low or undetectable levels of neural cell-adhesion mole cule (NCAM) antigen and DDC activity. N2+, one of the subclones of NCI -N417 cells, exhibited a higher type-I to type-II ratio after the cell s had adhered to a laminin-coated plate and had emitted neurite-like p rocesses. These findings provide evidence that alternative splicing pa tterns of NFI mRNA correlate with the mechanisms that regulate the gro wth patterns and neuroendocrine properties of SCLC cells in vitro. (C) 1995 Wiley-Liss, Inc.