Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-10-8
pubmed:abstractText
The transforming potential of the MDM2 oncogene has been attributed to the overproduction of the protein. In order to investigate regulation of MDM2 expression in head and neck squamous cell carcinomas, we analysed MDM2 gene amplification, and mRNA and protein expression in tumour specimens from 62 patients, in cell lines, and in normal epithelium adjacent to tumours or obtained from healthy patients. Additionally, TP53-induced MDM2-P2 transcription was evaluated and compared with TP53 status. MDM2 gene amplification and mRNA over-expression is infrequent, 7 and 9%, respectively. The predominant transcript codes for full-length MDM2 protein (90kD) and the level of alternatively spliced forms is not significant. We show that only 47% of tumours exhibit MDM2 immunostaining in more than one third of the neoplastic cells, and thus more than half of the tumours display no or low levels of MDM2 protein. In contrast, MDM2 protein is always detectable in basal and parabasal cells of morphologically normal epithelium outside the invasively growing tumour, as well as in a normal uvula sample. Similarly, the total amount of MDM2 transcripts analysed by reverse transcriptase-polymerase chain reaction is reduced in tumour samples compared to normal tissues, essentially due to a decrease in P2 transcript levels. The relationship between mutated p53 status and low levels of MDM2 found in cell lines is also observed to a certain extent in primary tumour samples. Overall, there is a high frequency of TP53 mutation and under-expression of MDM2 in the head and neck tumours. Moreover, a significant association of decreased MDM2 expression is observed with advanced tumour stage and 3 years survival.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1368-8375
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
620-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance.
pubmed:affiliation
Laboratoire de Biologie Tumorale, Centre Paul Strauss, 3 rue de la Porte de l'Hôpital, F-67085 - Strasbourg cedex, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't