cell expression

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cell expression

Post by KTK » Thu Apr 28, 2005 11:12 pm

How is it that over-expression of Myc can have such differnt outcomes innormal cells and cancer?
Last edited by KTK on Thu May 12, 2005 11:06 am, edited 3 times in total.

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Post by Chris4 » Fri Apr 29, 2005 9:25 am

Im not sure about your second question, but i'll have a go at the first one :D

This is a great website all about Myc which i am looking at now: http://www.myc-cancer-gene.org/.
I'll just copy stuff from there: The MYC cancer gene contains instructions for the production of the c-Myc protein. The c-Myc protein is now known as a transcription factor or a regulator of other genes. There are alternative translational initiation sites which result in both shorter and longer forms of the protein termed p67 Myc and MycS. But c-Myc is the main protein produced by Myc.

cells in which myc expression is specifically switched on independently of growth factors cannot enter G0, and if they are in G0 when Myc protein is provided, they will leave G0 and begin to divide even in the absence of growth factors - a behavior that ultimately causes them to undergo programmed cell death.

You've got to look at the differences between cancer cells and normal cells. Expression of c-myc in the normal cell is tightly regulated by external signals, such as growth factors and extracellular matrix contacts, as well as by internal clocks, such as the cell cycle. The resting cell normally expresses little c-myc, whereas cells stimulated by growth factors dramatically increase c-myc expression as an immediate early response gene. c-myc expression persists into the cell cycle, but then returns to its basal quiescent state in resultant resting daughter cells.
Abnormal or ectopic overexpression of c-myc in primary cells activates a protective pathway through the induction of p19/p14ARF and a p53-dependent cell death pathway. Hence, normal cells that overexpress c-myc are eliminated from the host organism through apoptosis, thereby protecting the organism from lethal neoplastic changes.
More than 50% of cancers contain a mutation in p53. Its disabled. The protective pathway (p53-dependent) which sends cells into apoptosis is therefore disrupted in cancer cells, which leads to excess cell proliferation and not apoptosis.
I'll copy a good explanation from here: http://www.springerlink.com/app/home/co ... 1:100124,1
The Myc family of oncoproteins promote cell growth and are frequently overexpressed in human tumors. However, Myc can also trigger cell death by apoptosis. This is at least in part mediated via the ARF-p53 pathway. Myc activation leads to a selection for inactivation of ARF or p53, allowing cell survival and tumor progression. Restoration of p53-dependent apoptosis by various means is an attractive approach for new cancer therapy.

So in short in cancer, the ARF-p53 pathway is inactivated and therefore apoptosis is not induced even if Myc is overexpressed.

I'd also like to mention, although a link between c-myc and cancer is well established both in vivo and in vitro, the molecular cellular mechanisms of c-myc-mediated transformation is not fully known.

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