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 corresponding to the gene's GTPase-activating protein-related domain (GRD). Relative expression levels of these 2 transcripts were previously correlated to neural differentiation. Since small-cell lung carcinoma (SCLC) often exhibits neuroendocrine properties, we analyzed the type-I to type-II mRNA ratio in 15 SCLC cell lines, using reverse transcriptase and polymerase chain reaction methods. The type-I mRNA was predominant 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 predominantly expressed type-II mRNA, adhered to the culture substrate, and expressed low or undetectable levels of neural cell-adhesion molecule (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 cells had adhered to a laminin-coated plate and had emitted neurite-like processes. These findings provide evidence that alternative splicing patterns of NFI mRNA correlate with the mechanisms that regulate the growth patterns and neuroendocrine properties of SCLC cells in vitro.
Koh
T
T
Department of Tumor Biology and Pathology, Faculty of Medicine, Kyoto University, Japan.
Yokota
J
J
Ookawa
K
K
Kina
T
T
Koshimura
K
K
Miwa
S
S
Ariyasu
T
T
Yamada
H
H
Osaka
M
M
Haga
H
H
D017398:Alternative Splicing / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D004296:Dopa Decarboxylase / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015816:Cell Adhesion Molecules, Neuronal; D007797:Laminin; D004296:Dopa Decarboxylase