| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
School of Dentistry and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90024
We previously immortalized human oral keratinocytes by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA and established two cell lines. These transfected cells were morphologically different from the normal counterpart, contained intact HPV-16 DNA in an integrated form, and expressed numerous viral genes. These cells contained lower levels of wild-type p53 protein and higher levels of c-myc mRNAs compared to normal cells. However, they proliferated only in keratinocyte growth medium containing a low level of calcium and were not tumorigenic in nude mice.
A HPV-16-immortalized cell line was exposed to either 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or N-methyl-N'-nitro-N-nitrosoguanidine. Four chemically transformed cell colonies were isolated. These cells proliferated well in Dulbecco's minimum essential medium containing a physiological level of calcium. They contained, similar to the immortalized counterpart, integrated HPV-16 sequences and lower levels of both wild-type p53 protein and DCC messages compared to normal cells. Among the chemically transformed cells, two colonies obtained from 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone exposure demonstrated an enhanced proliferation capacity in nude mice and transcribed a substantially higher amount of HPV-16 E6/E7, epidermal growth factor receptors, and c-myc genes compared with the immortalized counterpart. These experiments indicate that malignant transformation of oral keratinocytes can be caused by a sequential combined effect of "high risk" HPV and tobacco-related carcinogens.
1 Supported in part by USPHS Research Grant R01 DE10049 from the National Institute of Dental Research, NIH, and Grant 0231 from the Smokeless Tobacco Research Council, Inc.
2 To whom requests for reprints should be addressed, at Section of Oral Biology, UCLA School of Dentistry, 43-033 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90024.
Received 4/26/93. Accepted 8/11/93.
This article has been cited by other articles:
|
|
 |
|
  K.-J. Oh, A. Kalinina, N.-H. Park, and S. Bagchi Deregulation of eIF4E: 4E-BP1 in Differentiated Human Papillomavirus-Containing Cells Leads to High Levels of Expression of the E7 Oncoprotein J. Virol., July 15, 2006; 80(14): 7079 - 7088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Todd, P.W. Hinds, K. Munger, A.K. Rustgi, O.G. Opitz, Y. Suliman, and D.T. Wong CELL CYCLE DYSREGULATION IN ORAL CANCER Critical Reviews in Oral Biology & Medicine, January 1, 2002; 13(1): 51 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.K. Kang and M.-H. Park Conversion of Normal To Malignant Phenotype: Telomere Shortening, Telomerase Activation, and Genomic Instability During Immortalization of Human Oral Keratinocytes Critical Reviews in Oral Biology & Medicine, January 1, 2001; 12(1): 38 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fouret, G. Monceaux, S. Temam, L. Lacourreye, and J. L. Guily Human Papillomavirus in Head and Neck Squamous Cell Carcinomas in Nonsmokers Arch Otolaryngol Head Neck Surg, May 1, 1997; 123(5): 513 - 516. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Zhou, A. Lin, Z. Gu, S. Chen, N.-H. Park, and R. Chiu 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced c-Jun N-terminal Kinase (JNK) Phosphatase Renders Immortalized or Transformed Epithelial Cells Refractory to TPA-inducible JNK Activity J. Biol. Chem., July 21, 2000; 275(30): 22868 - 22875. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
