Transcriptional activation of H- and N-ras oncogenes in human cervical cancer.
OBJECTIVE
Overexpression of p21 protein has been detected in human cervical cancer. However, to date, there are no data on the differential activation of the three ras genes at the transcriptional level in cervical lesions. The purpose of this study was to evaluate the quantitative and qualitative changes of expression of the ras family genes in the development of human cervical cancer.


METHODS
The expression of ras mRNA levels in 35 human cervical specimens [11 normal cervix, 15 cervical intraepithelial neoplasia (CIN), 9 cervical cancer] was examined using the RT-PCR technique. In addition, we studied the incidence of point mutations in codon 12 of each ras gene using RFLP analysis and human papilloma virus (HPV) status.


RESULTS
The transcript levels for H-ras and N-ras were significantly higher in cancer cases compared to normal cervical tissues (P=0.0002 and P=0.001, respectively) and CIN lesions (P<0.0001 and P=0.002, respectively). The transcript levels for K-ras were similar in normal cervical tissue, CIN and cervical cancer. A strong positive correlation was found between H- and N-ras expression (P=0.001) and no correlation between H- and K- or N- and K-ras expression. Point mutations were detected only in three samples, located in codon 12 of K-ras gene. No relationship was found between expression levels of each ras gene and the presence of HPV.


CONCLUSIONS
Our findings indicate the expression pattern of the three ras genes in cervical tissue and the involvement of H- and N-ras up-regulation in the pathogenesis of cervical cancer independent of HPV infection.
Mammas
Ioannis N
IN
Laboratory of Virology, Medical School, University of Crete, Heraklion 71100, Crete, Greece.
Zafiropoulos
Alexandros
A
Koumantakis
Eugenios
E
Sifakis
Stavros
S
Spandidos
Demetrios A
DA
D000230:Adenocarcinoma / Q000235:genetics / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics; D017354:Point Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation; D014412:Tumor Virus Infections / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000821:virology
D004279:DNA, Viral; D012333:RNA, Messenger