The question is about their behavior in cell culture models. Considering cell proliferation & expression of certain invasion-related markers.
Thank you
Nees M, Geoghegan JM, Hyman T, Frank S, Miller L, Woodworth CD.Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappaB-responsive genes in cervical keratinocytes.J Virol. 2001 May;75(9):4283-96.
Cervical keratinocytes, as mentioned by Mohit Sharma, may reveal more profound changes by the HPV16 or 18 proteins E6 or E7 than epidermal keratinocytes because they are the natural target cells. So, skin keratinocytes (and in our hands the human keratinocyte cell line HaCaT) show comparable growth and differentiation behavior at least after transfection with with these viral genes. Irene Leigh and Birgit Lane, among others, have used this method to grow keratinocytes from normal skin or skin of patients suffering from blistering diseases, which also allowed to graft these cells.
The short answer is yes. Human keratinocytes that are transformed by HPV (HPV 16 or 18) behave very differently in certain ways than normal keratinocytes. HPV encoded proteins E6 and E7 target two major cell growth suppressors (p53 and pRb, respectively). Therefore, increased expression of these viral encoded proteins alters cell cycle regulation and, thus, cell proliferation. Additionally, HPV-transformed cells respond differently to a number of stress-induced stimuli.
Thanks all. Your feedback urged me to ask another question : CAN THEIR BEHAVIOR BE COMPARABLE TO SCC CELLS??
Fully agreeing with Divaker Choubey's comment, E6 and E7 will compromize cell cycle regulation by p53 and Rb which gives rise to cell immortalization but also allows the accumulation of genetic aberations on the long run. So, many altered cells are no longer eliminated from the actively proliferating cell pool. Concerning your second question, this per se will not create an SCC-like phenotype. Skin carcinogenesis is certainly a multi-step process, common to other types of human cancer. Thus, the forementioned cell line HaCaT , which is definitlively non-tumorigenic, caries two independent p53 mutations (involving both alleles). Most likely these mutations existed already in the pathologically 'healthy' skin sample of the donor (for more details see papers by P. Boukamp et al.). Nevertheless immortality seems to be among the first steps towards malignancy.
- Badges
- Science method