Tuesday, April 3, 2007

Cancer cells doing a Dolly: Rise of the cancer stem cells

One of the techniques employed to clone Dolly the Sheep from a differentiated cell is the use of the serum starvation technique. Serum starvation resulted in cells being starved of nutrients, which subsequently leads them to being arrested in the Go phase of the cell cycle that allows re-programming to take place (National Institute of Health). The milieu within a tumor is also similar, whereby nutrients is scarce.
After the step of cell cycle arrest, the nucleus is then introduced into an oocyte to allow nuclear reprogramming to take place. Scientists believe that the cytoplasm of oocytes contain proteins that encourage embryonic development. The notch, wnt and hedgehog pathways have stemness properties, yet they are also implicated in cancer. Aberrant activation of notch signaling has been implicated in human breast cancers (Stylianou et al, 2006). Wnt signaling has also been implicated in colorectal cancer (Bienz and Clevers, 2000). The hedgehog pathway has also been implicated in prostate cancer (Sheng et al, 2004). Exposure to the conditions of nutrient starvation resulting in cell cycle arrest and in addition to the pathways resulting in stemness characteristics such as the notch, Wnt and hedgehog, nuclear reprogramming can take place and we are looking at a fertile ground for the creation of the cancer stem cell through the evolutionary process (de Lau and Clevers, 2001).
Corrections: Added the words "through the evolutionary process" in the last sentence of the last paragraph.

Citations
1) National Institute of Health. http://science.education.nih.gov/home2.nsf/Educational+ResourcesTopicsGenetics/BC5086E34E4DBA0085256CCD006F01CB

2) Starve a Tumor, or Feed a Tumor? http://www.urmc.rochester.edu/pr/News/story.cfm?id=375

3) Stylianou S, Clarke RB, Brennan K. Aberrant activation of notch signaling in human breast cancer. Cancer Res. 2006 Feb 1;66(3):1517-25.

4) Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling. Cell. 2000 Oct 13;103(2):311-20.

5) Sheng T, Li C, Zhang X, Chi S, He N, Chen K, McCormick F, Gatalica Z, Xie J. Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer. 2004 Oct 13;3:29.

6) de Lau W, Clevers H. LEF1 turns over a new leaf. Nat Genet. 2001 May;28(1):3-4.

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