Two studies published today in the journal Genes & Development on August 1, 2010 gives the notion that cell death or apoptosis is not an absolute answer to getting rid of cancer cells. It turns out that cell death can actually sometimes spur the tumor growth.
The recent papers dealt with the role of a protein called PUMA, which triggers cell death in response to damaged DNA. PUMA is activated by the well-known tumour-suppressor protein p53, sometimes called ‘the guardian of the genome’. Without PUMA P53 cannot flip the cell-suicide ‘switching’. P53 senses the DNA damage and sends signals that activate PUMA, a potent proapoptotic BH3-only protein that inhibits all antiapoptotic proteins and activate the mitochondrial cytochrome C release leading to cell death.
Considering this in mind, the researchers developed mice that lack PUMA and then subjected those mice to DNA-damaging radiation. The researchers expected the animals to quickly develop cancer and die. But to their surprise the mice that lacked PUMA fared better than normal laboratory mice.
So whats happening? The researchers found out that PUMA producing mice activated cell death in response to DNA-damaging radiations, leading to creation of holes, that are now filled up by stem cells. But some of the stem cells retained the mutations caused to them by the radiation damage and they started to multiply causing cancers.
They are not sure if this works in humans also.But the results, if confirmed in humans, could have implications for cancer therapies now under development: some that aim to stimulate programmed cell death could actually stimulate cancer as well.
2. PUMA, a potent killer with or without p53- J Yu and L Zhang http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860432/