Two proteins are required for melanocyte stem cell maintenance and
the correct pigmentation throughout a mouse's life span.
Without these two proteins, mouse fur turns white.
Black Mouse White Mouse
Melanocytes are cells that give color to skin, fur and hair pigment while providing protection from the sun and lending organisms their color except when something goes wrong
Errors in melanocyte cells may lead to skin cancer known as melanoma, a highly aggressive cancer that becomes very difficult to treat as it develops and metastases.
Scientists at INSERM (Institut national de la santé et de la recherche médicale) published the results of their research in the review 'Cell Report' believing it paves the way stopping the formation of melanomas, the tumors that originate from melanocyte cells.
A few years ago, researchers discovered that, in humans, the B-Raf gene (coding gene for protein of the same name) is mutated in more than 50% of melanoma. Spectacular progress has been made in recent years in the treatment of this cancer, thanks to the development of pharmacological inhibitors that target an enzyme: the B-Raf kinase.
However, despite this discovery and its treatment, cancer returns in some patients, indicating that not all cancerous cells have been eliminated. This led the INSERM researchers to believe that B-Raf is not the only element driving the cancer process.
In new research, the scientists aimed to find out
how melanocytes normally function, inorder
to understand their specific role in cancer.
First they removed B-Raf protein, then,
C-Raf protein expression, from mice
with black fur (ideal to clearly seeing any
At first no changes in pigmentation
were observed for mice that had both
coding genes for B-Raf and C-Raf blocked
They had a normal color at birth.
they progressively lost hair
pigmentation as they grew to adults.
Turning grey from black, before
becoming increasingly white.
For Alain Eychène, the research team leader, "these observations represent a fault in melanocyte renewal. Since the color black is present at birth, the pigment cells clearly exist. However, the progressive whitening of the fur, once B-Raf and C-Raf have been removed from the cell line, proves that both these proteins are required for melanocyte renewal."
As is the case for all cells,
melanocytes originate from stem cells.
Stem cells are responsible for hair renewal
This research shows that it is specifically
this population of stem cells alone
that disappears progressively in mutant mice.
Alain Eychène: "This is the first in vivo
demonstration of the role of RAF proteins
in the self-renewal of stem cells."
As B-Raf and C-Raf proteins
are both involved in controlling
and renewing pigment stem cells,
this discovery represents another step
towards understanding and treating melanoma.
By blocking these proteins (using inhibitors) in patients undergoing treatment, it is possible that in time researchers will succeed in eliminating all cancerous stem cells, i.e. the likely cause behind cases of cancer reoccurrence.
B-Raf and C-Raf Are Requiredfor Melanocyte Stem Cell Self-Maintenance Agathe Valluet,1,2,3,4,6 Sabine Druillennec,1,2,3,4,6 Céline Barbotin,1,2,3,4 Coralie Dorard,1,2,3,4 Anne H. Monsoro-Burq,1,2,3,4Magalie Larcher,1,2,3,4 Celio Pouponnot,1,2,3,4 Manuela Baccarini,5 Lionel Larue,1,2,3,4 and Alain Eychène1,2,3,4,*
1Institut Curie 2INSERM U1021 3CNRS UMR 3347 Centre Universitaire, Orsay F-91405, France 4Universite´ Paris Sud-11, F-91405 Orsay, France 5Center for Molecular Biology, University of Vienna, Max F. Perutz Laboratories, A-1030 Vienna, Austria 6These authors contributed equally to this work
Cell Report http://dx.doi.org/10.1016/j.celrep.2012.08.020
Original article: http://www.eurekalert.org/pub_releases/2012-10/ind-awm100512.php