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BibTeX
Selective induction of apoptosis by leptomycin B in keratinocytes expressing HPV oncogenes
International journal of cancer, 2007-06, Vol.120 (11), p.2317-2324
Gray, Lindsey J.
Bjelogrlic, Predrag
Appleyard, Virginia C.L.
Thompson, Alastair M.
Jolly, Carol E.
Lain, Sonia
Herrington, C. Simon
2007
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Gray, Lindsey J.
Bjelogrlic, Predrag
Appleyard, Virginia C.L.
Thompson, Alastair M.
Jolly, Carol E.
Lain, Sonia
Herrington, C. Simon
Titel
Selective induction of apoptosis by leptomycin B in keratinocytes expressing HPV oncogenes
Ist Teil von
International journal of cancer, 2007-06, Vol.120 (11), p.2317-2324
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2007
Quelle
Wiley Online Library All Journals
Beschreibungen/Notizen
Human papillomavirus (HPV) infection is strongly associated with the development of anogenital neoplasia, particularly cervical cancer. It has been estimated that 99.7% of all cervical carcinomas are attributable to infection with HPV, and types 16 and 18 account for the vast majority of such cases. Both of these ‘high risk’ HPV types encode the oncoproteins E6 and E7, which exert multiple effects on many proteins involved in cell‐cycle regulation, including p53. The nuclear export protein inhibitor leptomycin B (LMB) has been shown to cause the nuclear sequestration of p53 in cervical carcinoma cells. We demonstrate that LMB induces apoptosis selectively at nanomolar concentrations in primary human keratinocytes (PHKs) expressing HPV oncogenes. Both monolayer and organotypic raft cultures of transduced PHKs were highly susceptible to treatment with LMB. By contrast, although LMB stimulated p53 accumulation in normal PHKs, no significant induction of apoptosis was detected on Western blots or immunostained monolayer/raft cells, or following pulsed exposure to the drug. Furthermore, topical application of μM concentrations of LMB to mouse skin was non‐toxic. These data suggest that the topical application of LMB to HPV‐infected intra‐epithelial lesions may represent a specific and effective therapeutic strategy against HPV‐associated anogenital neoplasia. © 2007 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0020-7136
eISSN: 1097-0215
DOI: 10.1002/ijc.22591
Titel-ID: cdi_proquest_miscellaneous_20678620
Format
–
Schlagworte
Antineoplastic agents
,
apoptosis
,
Apoptosis - drug effects
,
Biological and medical sciences
,
Blotting, Western
,
Cells, Cultured
,
Fatty Acids, Unsaturated - pharmacology
,
General aspects
,
Human papillomavirus
,
Humans
,
Immunohistochemistry
,
keratinocytes
,
Keratinocytes - cytology
,
Keratinocytes - drug effects
,
Keratinocytes - metabolism
,
Keratinocytes - virology
,
leptomycin B
,
Medical sciences
,
Oncogenes
,
Papillomaviridae - genetics
,
Pharmacology. Drug treatments
,
Tumors
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