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Expression of T‐type calcium channel splice variants in human glioma
Author(s) -
Latour Isabelle,
Louw Deon F.,
Beedle Aaron M.,
Hamid Jawed,
Sutherland Garnette R.,
Zamponi Gerald W.
Publication year - 2004
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20063
Subject(s) - glioma , biology , alternative splicing , exon , microbiology and biotechnology , human brain , gene isoform , cdna library , rna splicing , calcium channel , complementary dna , cancer research , rna , calcium , gene , genetics , neuroscience , medicine
In humans, three isoforms of the T‐type (Ca v 3.1) calcium‐channel α 1 subunit have been reported as a result of alternate splicing of exons 25 and 26 in the III–IV linker region (Ca v 3.1a, Ca v 3.1b or Ca v 3.1bc). In the present study, we report that human glioma express Ca v 3.1 channels in situ, that splicing of these exons is uniquely regulated and that there is expression of a glioma‐specific novel T‐type variant (Ca v 3.1ac). Seven human glioma samples were collected at surgery, RNA was extracted, and cDNA was produced for RT‐PCR analysis. In addition, three glioma cell lines (U87, U563, and U251N), primary cultures of human fetal astrocytes, as well as adult and fetal human brain cDNA were used. Previously described Ca v 3.1 splice variants were present in glioma samples, cultured cells and whole brain. Consistent with the literature, our results reveal that in the normal adult brain, Ca v 3.1a transcripts predominate, while Ca v 3.1b is mostly fetal‐specific. RT‐PCR results on glioma and glioma cell lines showed that Ca v 3.1 expression in tumor cells resemble fetal brain expression pattern as Ca v 3.1bc is predominantly expressed. In addition, we identified a novel splice variant, Ca v 3.1ac, expressed in three glioma biopsies and one glioma cell line, but not in normal brain or fetal astrocytes. Transient expression of this variant demonstrates that Ca v 3.1ac displays similar current‐voltage and steady‐state inactivation properties compared with Ca v 3.1b, but a slower recovery from inactivation. Taken together, our data suggest glioma‐specific Ca v 3.1 gene regulation, which could possibly contribute to tumor pathogenesis. © 2004 Wiley‐Liss, Inc.