Linked Life Data

15611226

Source:http://linkedlifedata.com/resource/pubmed/id/15611226

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-21
pubmed:abstractText
In this study, we describe the expression and function of CD40, a TNF receptor family member, in cervical carcinomas. CD40 was present at very low levels in normal cervical epithelium but was overexpressed in human papillomavirus-infected lesions and advanced squamous carcinomas of the cervix. The stimulation of CD40-positive cervical carcinoma cell lines with soluble CD40L (CD154) resulted in activation of the NF-kappaB and MAPK signaling pathways and up-regulation of cell surface markers and intracellular molecules associated with Ag processing and presentation. Concomitantly, the CD154-induced activation of CD40 in carcinoma cells was found to directly influence susceptibility to CTL-mediated killing. Thus, CD40 stimulation in cervical carcinoma cell lines expressing a TAP-dependent human papillomavirus 16 E6 Ag epitope resulted in their enhanced killing by specific CTLs. However, CD154 treatment of carcinoma cells expressing proteasome-dependent but TAP-independent Ags from the EBV-encoded BRLF1 and BMLF1 failed to increase tumor cell lysis by specific CTLs. Moreover, we demonstrate that chemotherapeutic agents that suppress protein synthesis and reverse the CD40-mediated dissociation of the translational repressor eukaryotic initiation factor 4E-binding protein from the initiation factor eukaryotic initiation factor 4E, such as 5-fluorouracil, etoposide, and quercetin, dramatically increase the susceptibility of cervical carcinoma cells to CD40L-induced apoptosis. Taken together, these observations demonstrate the functional expression of CD40 in epithelial tumors of the cervix and support the clinical exploitation of the CD40 pathway for the treatment of cervical cancer through its multiple effects on tumor cell growth, apoptosis, and immune recognition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
174
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15611226-Antigen Presentation, pubmed-meshheading:15611226-Antigens, CD40, pubmed-meshheading:15611226-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:15611226-Apoptosis, pubmed-meshheading:15611226-CD40 Ligand, pubmed-meshheading:15611226-Carcinoma, Squamous Cell, pubmed-meshheading:15611226-Cervical Intraepithelial Neoplasia, pubmed-meshheading:15611226-Female, pubmed-meshheading:15611226-Flow Cytometry, pubmed-meshheading:15611226-HeLa Cells, pubmed-meshheading:15611226-Humans, pubmed-meshheading:15611226-Immunoblotting, pubmed-meshheading:15611226-Immunohistochemistry, pubmed-meshheading:15611226-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:15611226-NF-kappa B, pubmed-meshheading:15611226-Papillomavirus Infections, pubmed-meshheading:15611226-Proteasome Endopeptidase Complex, pubmed-meshheading:15611226-Signal Transduction, pubmed-meshheading:15611226-T-Lymphocytes, Cytotoxic, pubmed-meshheading:15611226-Uterine Cervical Neoplasms
pubmed:year
2005
pubmed:articleTitle
Activation of CD40 in cervical carcinoma cells facilitates CTL responses and augments chemotherapy-induced apoptosis.
pubmed:affiliation
Cancer Research UK Institute for Cancer Studies and Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birhimgham B15 2TA, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't