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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-5-10
pubmed:abstractText
Pem, a member of homeobox genes, is an oncofetal gene which is preferentially expressed in reproductive tissues and in multiple tumor cell lines. However, the function of Pem in tumor cell lines has not been elucidated. Herein we report that the ectopic expression of Pem in TC-1, a human papillomavirus type 16 (HPV-16) E7-expressing surrogate cervical tumor cell line, demonstrated a significant increase in extracellular signal-regulated kinase (ERK) activity and multiple resistance to various apoptotic pressures from an E7-specific CD8(+) T cell-mediated immune response and anticancer drug treatment. The observed resistance to apoptotic death of the Pem-over-expressing TC-1 tumor cells (TC-1/Pem) was associated with the down-regulation of a pro-apoptotic molecule, such as BIM, and up-regulation of an anti-apoptotic molecule, such as Bcl-2 protein, which mediated ERK activation. We also observed that the intratumoral injection of an ERK inhibitor enhanced the therapeutic efficacy of E7-specific CD8(+) T cell adoptive transfer or anticancer drug treatment against the resistant TC-1/Pem tumor. This is the first evidence demonstrating an association between Pem and a signaling pathway, namely the ERK-mediated survival signal transduction pathway. Thus, our data indicate that activation of the ERK pathway represents a new mechanism of Pem-mediated multiple resistances and the present research will contribute to the development of a novel strategy in cancer therapy against Pem-over-expressing tumor cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1872-7980
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Pem renders tumor cells resistant to apoptotic cell death induced by a CD8+ T cell-mediated immune response or anticancer drug treatment.
pubmed:affiliation
Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't