Identification of novel molecular markers which correlate with HPV-induced tumor progression.
High risk HPVs (human papillomaviruses) are causally involved in the development of cervical cancer. However, other factors, such as somatic genetic alterations also play a decisive role in malignant conversion of cervical keratinocytes. Mutations and chromosomal aberrations are known to influence the pattern of gene expression. Therefore we used the recently developed RT-PCR based method of differential display of mRNAs to detect differences in gene expression which correlate with tumorigenicity. Non-tumorigenic HPV16-immortalized human foreskin keratinocytes (HPK IA) were compared with their tumorigenic counterparts and 49 different genes were identified which were either up- or downregulated. The identified genes encode proteins of the cytoskeleton and the extracellular matrix, the nuclear splicing apparatus, transcription regulators and membrane-associated proteins. The expression pattern of all genes was also examined by RNA-RNA in situ hybridization in biopsies of normal cervical epithelium, precancerous lesions and cancers. Two genes, C4.8 and C21.7, are of particular interest because their expression is upregulated in a subset of high grade precancerous lesions and in over 58% of cancers. These two genes may therefore be considered as putative progression markers. C4.8 is a new member of the transmembrane 4 (TM-4) protein family which includes tumor-associated antigens such as CD63 and TAPA-1, whereas C21.7 shows no significant homologies to any known genes or proteins.
Nees
M
M
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
van Wijngaarden
E
E
Bakos
E
E
Schneider
A
A
Dürst
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002584:Cervix Uteri / Q000473:pathology; D004273:DNA, Neoplasm; D018450:Disease Progression; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000503:physiopathology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014412:Tumor Virus Infections / Q000235:genetics* / Q000503:physiopathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000503:physiopathology
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm