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[P83A]: PKCδ as a moelcular switch in the apoptosis and survival of glioma cells
Author(s) -
Okhrimenko H.,
Lu W.,
Xiang C.,
Gomel R.,
Blass M.,
Brodie C.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.145
Subject(s) - citation , library science , classics , history , computer science
tion what happens if the cells with self-renewal capacity are exposed to viral oncogenes. We studied how oncogenes and tumor suppressors affect the differentiation capacity, proportion and characteristics of progenitor cells in a model tissue. For this we used neural progenitor cells (NPCs) transduced with modified retroviruses carrying Human Papilloma Virus E6, E7 or E6/E7 oncogenes. HPV 16 E6/E7 is a classical oncogene complex, which degrades tumor suppressors p53 and pRb/p107/p130 and interferes with several other cellular activities. To examine further p53 and pRb involvement in NPC maintenance, we used p53−/− and E7 and E6/E7− expressing NPCs with restored pRb expression, respectively. E6/E7 expressing or p53−/− NPCs were able to differentiate, but simultaneously retained high capacity for self-renewal, proliferation, ability to remain multipotent in conditions promoting differentiation, and showed delayed cell cycle exit. These functions were mediated through p53 and pRb family and involved MEK-ERK signaling. Low amount of p53 increased self-renewal and proliferation, where as pRb affected only proliferation. This suggests that the oncogenes increase, while p53 and pRb-family tumor suppressors decrease the number and proportion of progenitor cells. These findings provide one explanation how oncogenes and tumor suppressors control tissue homeostasis and highlight their importance in stem cell selfrenewal, linked both to cancer and life-long tissue turnover.