Regular Article

British Journal of Cancer (2001) 84, 374–380. doi:10.1054/bjoc.2000.1615 www.bjcancer.com
Published online 30 January 2001

Metastatic MHC class I-negative mouse cells derived by transformation with human papillomavirus type 16

M S caronmahel1, E Sobotková1, J Bubeník2, J S caronímová2, R Z caronák1, V Ludvíková1, R Hájková2, J Kovar caroník4, F Jelínek1, C Povýs caronil3, J Marinov1 and V Vonka1

  1. 1Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic
  2. 2Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 166 37 Prague 6, Flemingovo nám. 2, Czech Republic
  3. 3Second Institute of Pathology, 1st Medical Faculty, Charles University, U nemocnice 4, 128 20 Prague 2, Czech Republic
  4. 4Department of Cellular and Molecular Oncology, Masaryk Memorial Cancer Institute, Z caronlutý kopec 7, 656 53 Brno, Czech Republic

Received 31 May 2000; Revised 14 October 2000; Accepted 17 October 2000.

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Abstract

In the endeavour to develop a model for studying gene therapy of cancers associated with human papillomaviruses (HPVs), mouse cells were transformed with the HPV type 16 (HPV16) and activated H-ras oncogenes. This was done by contransfection of plasmid p16HHMo, carrying the HPV16 E6/E7 oncogenes, and plasmid pEJ6.6, carrying the gene coding for human H-ras oncoprotein activated by G12V mutation, into secondary C57BL/6 mouse kidney cells. An oncogenic cell line, designated MK16/1/IIIABC, was derived. The epithelial origin of the cells was confirmed by their expression of cytokeratins. No MHC class I and class II molecules were detected on the surface of MK16/1/IIIABC cells. Spontaneous metastases were observed in lymphatic nodes and lungs after prolonged growth of MK16/1/IIIABC-induced subcutaneous tumours. Lethally irradiated MK16/1/IIIABC cells induced protection against challenge with 105 homologous cells, but not against a higher cell dose (5 times 105). Plasmids p16HHMo and pEJ6.6 were also used for preventive immunization of mice. In comparison with a control group injected with pBR322, they exhibited moderate protection, in terms of prolonged survival, against MK16/1/IIIABC challenge (P < 0.03). These data suggest that MK16/1/IIIABC cells may serve as a model for studying immune reactions against HPV16-associated human tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords:

human papillomavirus, E6/E7 oncogenes, cell transformation, tumour-cell vaccine, DNA vaccine, H-ras

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