For day 2 of Experimental Biology, I found an interesting poster on a new chemical, found in slime mold, that might have therapeutic potential for breast cancer treatment! Enjoy!
We are always looking for new cancer treatments. Each type of cancer is different, from breast cancer to lung cancer or pancreatic, and there are also different subtypes of cancers within each type of cancer. Your breast cancer can be estrogen receptor positive or negative, and this can drastically effect what kind of treatments may work best. And new treatments can come from the oddest places.
In this case, the odd new treatment is a chemical called Dif-1, a chemical usually found in the slime mold Dictyostelium discoideum. (http://en.wikipedia.org/wiki/Slime_mold).
In the slime mold, Dif-1 is a morphogen, a chemical that controls the path of cellular development. In Dichty, Dif-1 causes reproductive stalk formation. But it may do more than that. Other laboratories have reported that Dif-1 might have anticancer properties, stopping cancer cells from proliferating (Mori, 2005: http://www.ncbi.nlm.nih.gov/pubmed/16153639, Gokan, 2005: http://www.ncbi.nlm.nih.gov/pubmed?term=dif-1%20gokan%202005). In this study, Bratton et al from Tulane University wanted to investigate how, exactly, Dif-1 might be acting to inhibit cancer cell proliferation. They hypothesized that the estrogen receptor might be involved.
To look at this, Bratton et al examined the activity of Dif-1 in a line of breast cancer cells (MCF-7) that express the estrogen receptors alpha and beta. In general, cells with estrogen receptors will proliferate in response to estrogen. So you can plate cells, add estrogen, and watch the cells grow. But when Bratton added Dif-1 to these cells, they found that the effects of estrogen were blocked, the cells could not proliferate. It looks like Dif-1 inhibits breast cancer cell proliferation, perhaps via an estrogen receptor based mechanism.
But how was this working? Bratton et al used a luciferase assay, which allows you to link a luminescent protein to a piece of DNA to which the ER binds.. When there is more active ER protein, you get more glow. In the presence of estrogen, the ER alpha receptor was activated, resulting in a bright glow, but not in the presence of Dif-1.
And the inhibition of estrogen receptors went further, estrogen receptor mRNA expression was down and downstream proteins like the progesterone receptor also showed decreased expression in the presence of Dif-1. But it doesn’t seem like Dif-1 is having its effects by directly inhibiting the estrogen receptor. If that were the case, estrogen receptor mRNA levels would not be affected. So where is Dif-1 acting? Bratton et al discovered that Dif-1 is acting at the promotor region of the estrogen receptor gene, which can control whether or not the gene is transcribed to mRNA. By interacting with the promotor (either directly or by activating a promoter binding protein), Dif-1 can repress gene transcription activity. When estrogen receptor mRNA is repressed, you get reduced amounts of estrogen receptor protein. And with less estrogen receptor, breast cancer cells cannot grow as well in response to estrogen. This could be how Dif-1 is working to prevent the growth of breast cancer cells, and it could be another way to treat certain types of breast cancer which depend on estrogen receptor alpha expression. Not too bad for a chemical from a slime mold!