Expression of cellular genes in HPV16-immortalized and cigarette smoke condensate-transformed human endocervical cells.
We studied the molecular mechanism of successive multistep cervical carcinogenic progression with our previously established in vitro model system. This system was composed of primary human endocervical cells (HEN), two lines of HEN immortalized by HPV16 and their counterparts subsequently malignantly transformed by cigarette smoke condensate (CSC). The expression was examined of diverse cellular genes associated with oncogenesis and senescence, especially for cervical cancer. Consistent results were seen for the pairs of immortalized and malignantly transformed lines. Immortalization of HEN by HPV16 resulted in enhanced expression of H-ras, c-myc, B-myb, p53, p16INK4 and PCNA mRNA; enhanced expression of p16 and PCNA proteins; decreased expression of WAF1/p21/Cip1/Sid1 and fibronectin mRNA; and decreased p53 protein. On the other hand, the CSC-transformed counterparts of HPV16-immortalized cells had up-regulated levels of B-myb, p53 and WAF1 mRNA and p53 protein. Our results indicate that the differential activation or inactivation of multiple cellular genes is important for the immortalization, as well as the transformation, of human cervical cells. Further, we suggest that our in vitro model system is useful for investigating the molecular mechanism of multistep cervical carcinogenesis.
Yang
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X
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Nakao
Y
Y
Pater
M M
MM
Tang
S C
SC
Pater
A
A
D000199:Actins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D009857:Oncogenes; D027383:Papillomaviridae / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012906:Smoke / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D000097642:GADD45 Proteins
D000199:Actins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D012906:Smoke; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins; C493956:CDKN1A protein, human; C497206:MDM2 protein, human