The development of larger cells that spontaneously escape senescence - a step during the immortalization of a human cancer cell line

Abstract There are few information concerning the changes associated with the transition interval when slow growing, pri-mary explanted human cancer cells are displaced by new selected faster growing cells and became an immortal cellline. In a previous paper ( J. Cell. Mol. Med. , 5 : 49-59, 2001) we described the TV cell line derived from a laryngealtumor which harbors human papillomavirus (HPV) gene sequences throughout more than sixty in vitro passages. Inthis paper we analyze the modifications observed during the crisis interval when significant amount of cells senescebut occasional cells acquire some mutations that make them immortal. Confocal microscopy analysis revealed theheterogeneity of the cells in terms of their size and nucleus/cell ratio. Proliferation capacity was assessed by flowcytometry analyzing DNA content and expression of transferrin receptor (CD71). We discussed the possibility thatHPV genome sequences alleviate a proliferation block during the crisis growth arrest of human larynx carcinoma cellline and the possibility that the cells monitor their size and growth by measuring the levels of some protein whosesynthesis is coupled to cell development.