eileen

Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR knock-down

Jose L Costa , Paul P Eijk , Mark A van de Wiel , Derk ten Berg , Fernando Schmitt , Carmen J Narvaez , JoEllen Welsh and Bauke Ylstra
BMC Genomics 2009, 10:499doi:10.1186/1471-2164-10-499
Published:28 October 2009
Abstract (provisional)


Background

The active form of Vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), has strong anti-proliferative effects, yet the molecular mechanisms underneath this effect remain unclear. In contrast, the molecular mechanism of 1,25D for the regulation of calcium homeostasis has principally been resolved, demonstrating a pivotal role for the vitamin D receptor (VDR).
Results

We first addressed the question whether the anti-proliferative effects of 1,25D are influenced by VDR. Knockdown of VDR by siRNA did not affect the anti-proliferative effects of 1,25D in MCF7 breast cancer cells. This unanticipated finding led us to take an alternative approach using genome wide screens to study the molecular mechanisms of 1,25D in proliferation. For that purpose, four independently developed and stable 1,25D resistant MCF7 cell lines were analyzed. Array CGH identified a copy number alteration in a region of 13.5 Mb at chromosome 11q13.4-14.1 common to all four 1,25D resistant cell lines. Expression arrays revealed that no single gene was differentially expressed between the sensitive and resistant cells, but multiple membrane receptor signaling pathways were altered in the 1,25D resistant cell lines. Importantly, in the genome wide experiments neither VDR, CYP24A1 nor other known vitamin D signaling pathway genes were associated with 1,25D resistance.
Conclusion

In conclusion, siRNA and genome wide studies both suggest that the anti-proliferative effects of 1,25D in MCF7 breast tumor cell lines do not rely on classical Vitamin D pathway per se.

Source Link: http://www.biomedcentral.com/1471-2164/10/499/abstract

Full Report PDF File Link: http://www.biomedcentral.com/content...164-10-499.pdf

__________________
"under exposure to UV rays is as dangerous as overexposure....this is D life" eileen

CrystalSS

Ummmm..Yah...I will get right back to you.

MicroSpa

First - Proliferation means - To grow or multiply by rapidly producing new tissue, parts, cells, or offspring.

Not good for cancer cells.

Anti would be the opposite which D3 apparently does. A good thing

siRNA is involved in the RNA interference (RNAi) pathway, where it interferes with the expression of a specific gene. Something the scientists use in testing.

If they were introducing sirna to D3 and D3 still had the Anti-proliferation properties after it was introduced, then they are saying that D3 does not rely on the typical gene pathways as others do. That is what is interesting about the study and it clearly shows that the medical community does not understand D3 or it's potential cancer cell muting effects.

They just tried to interfere with it using a known or standardly used process and it didn't work. D3 still retained it's properties.

MicroSpa

Very interesting when you read through the pdf after you understand the terminology.

Here's the conclusion that I think everyone will understand from the detailed report.

Conclusion
Evidence accumulates demonstrating an important role for Vitamin D not only in the treatment but also in the prevention of cancer, mainly breast cancer. Dozens of vitamin D analogues have been developed by pharmaceutical firms with the goal of dissociating the potentially toxic calcemic actions of 1,25D from its anti-tumor actions for use in cancer therapy. Because vitamin D analogs are currently in approximately 20 clinical trials [2], understanding the mechanisms by which 1,25D mediates growth inhibition, as well as the basis for development of 1,25D resistance, is crucial. Our genome wide screening analysis has
identified chromosomal regions, membrane receptor pathways and new candidate genes outside of the classical VDR signaling pathway that may be associated with 1,25D resistance. These data provide new avenues for future explorations that may facilitate the development and use of vitamin D based drugs for cancer and other clinical applications.

DB Hottie

Where's the sunshine in vitamin D based drugs, cancer, clinical applications?

I need to reread the article, there is a ball bouncing around in my head.

__________________
Find your zipper

MicroSpa

Another interesting point from the study.

The challenge with vitamin d3 based drugs is that they have found challenges with controlling calcium levels. Not a good thing.

They mention in the study that d3 is produced from within and since they don't completely understand how it works(they do seem to understand it's benefits), drug companies are having a hard time creating drugs that fight cancer and don't unbalance calcium levels.

I guess the point there is Naturally is the best way.

CrystalSS

Great interpretation Chris!

unity

Very interesting. I knew about D, learned about D3 and now I find it even more amazing.

__________________
OMG! I made a post! :)

Neon Beach

Take some supplements and forget about it.

__________________

eileen

^ who let you out to play? i hope you can handle the big dogs :P

__________________
"under exposure to UV rays is as dangerous as overexposure....this is D life" eileen