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 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.
Oguro-Okano
M
M
Department of Immunology, Mayo Clinic, Rochester, MN 55905.
Griesmann
G E
GE
Wieben
E D
ED
Slaymaker
S J
SJ
Snutch
T P
TP
Lennon
V A
VA
D001483:Base Sequence; D015152:Blotting, Northern; D015220:Calcium Channels / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015220:Calcium Channels