Molecular diversity of neuronal-type calcium channels identified in small cell lung carcinoma

Using the polymerase chain reaction (PCR), we identified RNA transcripts for two distinct classes of neuronal-type voltage-gated Ca2+ channels (VGCC) in a prototypic small cell lung carcinoma (SCLC) cell line, SCC-9. Oligonucleotide primers were designed to encode amino acid sequences common to alph...

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Bibliographic Details
Published in:	Mayo Clinic proceedings Vol. 67; no. 12; p. 1150
Main Authors:	Oguro-Okano, M, Griesmann, G E, Wieben, E D, Slaymaker, S J, Snutch, T P, Lennon, V A
Format:	Journal Article
Language:	English
Published:	England 01-12-1992
Subjects:	Base Sequence Blotting, Northern Calcium Channels - genetics Carcinoma, Small Cell - metabolism Cloning, Molecular Humans Molecular Sequence Data Neuroblastoma - metabolism Neurons - metabolism Polymerase Chain Reaction Rhabdomyosarcoma - metabolism Tumor Cells, Cultured
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Summary:	Using the polymerase chain reaction (PCR), we identified RNA transcripts for two distinct classes of neuronal-type voltage-gated Ca2+ channels (VGCC) in a prototypic small cell lung carcinoma (SCLC) cell line, SCC-9. Oligonucleotide primers were designed to encode amino acid sequences common to alpha 1-subunits of known neuronal VGCC classes. Sequencing of complementary DNA (cDNA) clones derived from two independent PCR products revealed that one corresponded to a brain class A VGCC fragment predicted to encode a P-type VGCC (insensitive to dihydropyridines and omega-conotoxin) characteristic of cerebellar Purkinje cells but not previously identified in humans. The second PCR product was identical (except for one conservative nucleotide difference) to a fragment of the class D VGCC of neurons and neuroendocrine cells, which encodes an L-type VGCC (sensitive to dihydropyridines). By Northern blot analyses, both cDNAs hybridized to messenger RNAs (mRNAs) obtained from SCC-9; class D hybridized additionally to human cerebral cortical mRNA, but neither hybridized to mRNA from the skeletal muscle cell line TE671. Although no cDNA corresponding to class B VGCC (N-type) was identified, SCLCs are known to express VGCC that are sensitive to omega-conotoxin and coprecipitate with 125I-labeled-omega-conotoxin when complexed with serum IgG from patients with the Lambert-Eaton myasthenic syndrome. The multiple classes of neuronal-type VGCC expressed in SCLC could conceivably have both unique and related antigenic determinants that may give rise to antineuronal autoimmune responses. This would account for a spectrum of paraneoplastic neurologic disorders including the Lambert-Eaton syndrome and subacute cerebellar degeneration.
ISSN:	0025-6196
DOI:	10.1016/S0025-6196(12)61144-6