Cell Biology; Gene causing tumors by "double-whammy" mechanism also reveals the key to a cure
Posted on: Tuesday, 10 February 2004, 06:00 CST
2004 FEB 10 - (NewsRx.com & NewsRx.net) -- Scientists at the Babraham Institute have discovered that a tiny change in a protein involved in cell survival is responsible for abnormal cell activity in the early stages of cancer.
The protein, known as Bcl-xL, normally protects cells from dying; and when the DNA in cells becomes damaged, Bcl-xL is modified so that it no longer keeps the cells alive. Hence, the cells with damaged DNA usually die, so preventing them from becoming cancer cells.
However, in the presence of a particular cancer gene, the usual modification of Bcl-xL following DNA damage doesn't occur, so cells with DNA damage are kept alive, resulting in cancer.
The discovery, described in an article in Cancer Cell, was made by Dr. Rui Zhao, working in Dr. Denis Alexander's research group at the Babraham Institute, Cambridge. Zhao noticed that the tiny change in Bcl-xL that normally occurs after exposing cells to radiation no longer happened when the particular cancer gene was present. "The cancer model that we're working on is T-cell lymphomas", Alexander explained, "but it's quite likely that this mechanism could be relevant to other types of cancer as well - 24,500 people in Britain every year are diagnosed with a cancer of the blood".
Intriguingly, the cancer gene being studied at the Babraham Institute (a hyperactive tyrosine kinase) acts by a "double-whammy" mechanism. In the first instance, it inhibits the rapid repair of DNA damage that often occurs as cells divide. Therefore DNA damage quickly begins to accumulate in cells containing the cancer gene. Additionally, the cancer gene prevents the cells with damaged DNA from being eliminated, so leading to cancer. "It is quite likely", said Alexander, "that if only one of these mechanisms were taking place, there would be no cancer. It's when both occur simultaneously, the 'double-whammy', that the catastrophe happens."
Understanding how the cancer gets going in the first place might eventually lead to novel cancer therapies. Alexander's group has also shown that the critical modification of Bcl-xL, prevented by the cancer gene even before the cancer gets started, also remains blocked in tumors even when they've been exposed to reagents used in chemotherapy. "If we could find a way of averting this blockade", Alexander noted, "then the power of Bcl-xL in keeping tumour cells alive would be destroyed, and the tumor would either spontaneously die or would at least become more sensitive to chemotherapy or radiotherapy" (Zhao R, Yang FT, Alexander DR, et al., An oncogenic tyrosine kinase inhibits DNA repair and DNA damage-induced Bcl-xL deamidation in T cell transformation. Cancer Cell, 2004;5:37-59).
This article was prepared by Cancer Weekly editors from staff and other reports. Copyright 2004, Cancer Weekly via NewsRx.com & NewsRx.net.
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