Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Loss of amino acids 1490Lys-Ser-Lys1492 in the COOH-terminal region of topoisomerase IIalpha in human small cell lung cancer cells selected for resistance to etoposide results in an extranuclear enzyme localization

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. A large-cohort, longitudinal study determines pre-cancer disease routes across different cancer types

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

The human small cell lung cancer NCI-H69 cell line selected for resistance to etoposide (H69/VP) has been reported previously to sequentially overexpress both the MRP and MDR1 multidrug resistance-conferring genes. In addition, immunocytochemistry of H69/VP cells demonstrated a distinct extranuclear localization of the nuclear enzyme topoisomerase IIalpha, the target of etoposide. Immunoblots showed a decrease in Mr 170,000 topoisomerase IIalpha in nuclear extracts in H69/VP but equal amounts of the enzyme in whole-cell extracts. Topoisomerase II catalytic activities in H69 and H69/VP whole-cell extracts were equal, as were their inhibition by etoposide. Sequencing of the entire H69/VP topoisomerase IIalpha cDNA showed a homozygous 9-nucleotide deletion encompassing nucleotides 4468-76, coding for Lys-Ser-Lys, overlapping two potential bipartite nuclear localization signals. The deletion occurred at the initial nine nucleotides of an exon, suggesting alternative splicing of topoisomerase IIalpha mRNA. Subsequent sequencing of H69/VP genomic DNA revealed a G-->T point mutation in the 3' acceptor splice site consensus sequence, resulting in the use of an alternate splice site. Comparison with previous reports on three drug-resistant cell lines with large truncations/deletions in the COOH-terminal region of topoisomerase IIalpha and extranuclear localization point to a pivotal role for the basic cluster 1490Lys-Ser-Lys1492 in the nuclear import of this enzyme.

OriginalsprogEngelsk
TidsskriftCancer Research
Vol/bind57
Udgave nummer20
Sider (fra-til)4451-4
Antal sider4
ISSN0008-5472
StatusUdgivet - 15 okt. 1997

ID: 59178485