Cancer is generally considered to be an abnormal growth of cells caused by
mutations in DNA induced by carcinogenic substances, viral oncogenes, ionizing
radiations etc. Although evidence has been insufficient, and it has also been
argued that often this relationship was not seen, the mutational theory of
cancer is the explanation we find in every textbook. A recent experiment raises
doubts about the validity of the dogma. Investigators show that mutation in the
Ha-ras-1 gene is sometime found in normal mammary gland and is absent in
cancerous cells. Here is the abstract published in the Journal of Cell Science
on March , 2 2004.

THE STROMA AS A CRUCIAL TARGET IN RAT MAMMARY GLAND CARCINOGENESIS
 
Maricel V. Maffini1, Ana M. Soto1,*, Janine M. Calabro1, Angelo A. Ucci2 and
Carlos Sonnenschein1 

A complex network of interactions between the stroma, the extracellular matrix
and the epithelium drives mammary gland development and function. Two main
assumptions in chemical carcinogenesis of the mammary gland have been that
carcinogens induce neoplasia by causing mutations in the DNA of the epithelial
cells and that the alterations of tissue architecture observed in neoplasms are
a consequence of this primary mutational event. Here, we use a rat mammary
tissue recombination model and the chemical carcinogen N-nitrosomethylurea
(NMU) to determine whether the primary target of the carcinogen is the
epithelium, the stroma or both tissue compartments. Mammary epithelial cells
were exposed in vitro either to the carcinogen or vehicle before being
transplanted into the cleared fat pads of rats exposed to carcinogen or
vehicle. We observed that neoplastic transformation of these mammary epithelial
cells occurred only when the stroma was exposed in vivo to NMU, regardless of
whether or not the epithelial cells were exposed to the carcinogen. Mammary
epithelial cells exposed in vitro to the carcinogen formed phenotypically
normal ducts when injected into a non-treated stroma. Mutation in the Ha-ras-1
gene did not correlate with initiation of neoplasia. Not only was it often
found in both cleared mammary fat pads of vehicle-treated animals and intact
mammary glands of untreated animals, but it was also absent in some tumors. Our
results suggest that the stroma is a crucial target of the carcinogen and that
mutation in the Ha-ras-1 gene is neither necessary nor sufficient for tumor
initiation.


I am not predicting (although I am not excluding) that this will start a chain
reaction of experiments designed to prove the EPIGENETIC origin of cancer, but
it should make us rethink what is real (production of proteins) and what is
fictious (determination of morphology, etiology of diseases, etc.) on the role
of genes in biology.
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