Cancer
Over the past few years, researchers have discovered that naturally-occurring
molecular snippets called "microRNAs" influence normal human growth
and development. In 2005, CSHL scientists Greg Hannon, Scott Lowe, Scott Powers
and their colleagues discovered that microRNAs can also play an important role
in cancer.
It is a remarkable example of the progress that can be made when researchers
working from different approaches collaborate closely on a project (in this case
Hannon, Lowe, and Powers working on microRNAs, animal models of cancer, and cancer
genomics, respectively).
The study focused on a segment of human chromosome 13 that was known to be "amplified" or
present in excess copies in several tumor types including B-cell lymphoma. The
researchers observed that five microRNAs encoded by this DNA segment—referred
to as the "mir-17-92 cluster"—are present at abnormally high
levels in human B-cell lymphoma cell lines as well as in biopsies of human lymphomas
and colorectal carcinomas.
Those discoveries indicated that misregulated microRNAs might contribute to human
cancer, particularly to B-cell lymphoma, but also to other forms of the disease.
To test whether increased levels of the microRNAs could indeed contribute to
cancer, the researchers engineered mouse cells to have high levels of the microRNAs.
They found that the microRNAs accelerated tumor development and decreased survival
in a mouse model of B-cell lymphoma.
Moreover, lymphomas engineered to have high levels of the microRNAs consistently
invaded organs including liver, lung, and kidney and lacked the extensive "programmed
cell death" which otherwise keeps tumors in check. The observations suggest
that the microRNAs promote metastasis.
The Cancer Genome Atlas pilot project recently announced by the National Cancer
Institute, in response to the recommendations of an NCI advisory committee of
which I was a member, aims to find all the major human cancer genes in specific
types of cancers. Now, with the knowledge that genes encoding RNA can be among
the set that promote cancer, the Cancer Genome Atlas has additional challenges
to discover how wide spread is this phenomenon.
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In other work aimed at investigating cancer progression, Alea Mills and her colleagues
have discovered that the loss of a gene called p63 accelerates aging in mice.
Similar versions of the gene are present in many organisms, including humans.
The p63 gene is thus likely to play a fundamental role in aging. |
Aging and cancer are two sides of the same coin. In one case, cells stop dividing.
In the other, they can't stop dividing. Therefore, Alea suspects that having
the right amount of the p63 protein in the right cells at the right time normally
creates a balance that enables organisms to live relatively cancer-free for a
reasonably long time.
To study how the p63 gene works, the researchers devised a system for eliminating
it from adult mouse tissues. What struck them right away was that the p63 deficient
mice were aging prematurely. The effects of premature aging observed in these
mice were hair loss, reduced fitness and body weight, progressive curvature of
the spine, and shortened lifespan.
The p63 gene has been studied since it was discovered in 1997, but this is the
first time it has been implicated in aging. A related protein called p53 is perhaps
the most commonly mutated gene in human cancers and acts to suppress tumor formation.
Both p63 and p53 bind to specific sequences in DNA and thus the interplay between
them, as well as a third related protein p73, may set up a regulatory network
that creates a balance between aging and cancer progression. |
