Cycling up the epidermis: reconciling
100 years of debate.
Alberto
Gandarillas1,2,* and Ana Freije1
Unformated preview in
http://onlinelibrary.wiley.com/doi/10.1111/exd.12287/abstract
ABSTRACT
There is likely general
consensus within the skin research community that cell cycle control is critical
to epidermal homeostasis and disease. The current predominant model proposes
that keratinocytes switch off DNA replication and undergo cell cycle and cell
growth arrest as they initiate terminal differentiation. However, this model
cannot explain key physiological features of the skin, mainly why squamous
differentiation prevails over proliferation in benign hyperproliferative disorders.
In recent years we have p roposed an
alternative model that involves mitotic slippage
and endoreplication. This new model is controversial and has encountered
resistance within the field. However, looking back at history, the epidermal
cell cycle has been a matter of controversy and debate for around 100 years
now. The accumulated data are confusing and contradictory. Our present model
can explain and reconcile both old and new paradoxical observations. Here we
explain and discuss the endoreplicative cell cycle, the evidence for and
against its existence in human epidermis and the important implications for
skin homeostasis and disease. We show that regardless of the strengths or
weaknesses of the Endoreplication Model, the existing evidence in support of the
Cell Cycle Arrest Model is very weak.
Keywords:
DNA damage – MYC - endocycles – cancer –carcinoma
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