Arianne Alcantara
September 3, 2013

Inhibition of FGF8b Protein Oncogenic Characteristics through Nucleic Acid Aptamer Selection

Prevalent throughout the world and always seemingly one step ahead of society’s most brilliant physicians, cancer has continued to ravage the human population for centuries. As a result, oncology methods to combat the disease seem to shift every year, with experts believing surgery to be the solution in the eighteenth century, to radiation, chemotherapy, and targeted therapy as alternatives in the twenty-first ("Evolution of Cancer Treatments," 2012).  The protein present in humans, Fibroblast Growth Factor 8 (FGF8), can be attributed directly to the third of the aforementioned techniques, targeted therapy, due to its significant role in cell processes such as mitogenesis and angiogenesis. Its isoform FGF8b is medically known as an androgen-induced on dominant in tumorigenesis and hormonal carcinogenesis, with one of the more popular diseases being prostate cancer (Henderson and Feigelson, 1999).
Although FGF8b expression is linked to hormone-related cancers, speculation still remains as to whether it is the cause; furthermore, like all proteins, FGF8 performs various other functions such as those pertaining to embryo development, tissue repair, and cell survival (White and MacArthur, 1995). Consequently, recognizing its role in human development forces the necessary realization that completely eradicating the protein will produce more harmful side effects than good ones. Employing more selective techniques designed to inhibit FGF8 after a certain point instead of abolishing it are sought in this study.

Figure 1 illustrates the affect of an RTK inhibitor if a growth factor like FGF8, binds to a cell. The discovery of an FGF8b aptamer would lead to the prevention of a possibly cancerous cell to divide, and as such remain benign ("Cancer Growth Blockers," 2013).

Specific Aim 1: Employing therapeutic strategies, to determine an aptamer, substance with the capability to bind to a target molecule, through bead-based selection for FGF8 that once bound together, possesses the ability to trigger inhibition or at least antagonization and alter the protein’s affects on an organism.

Specific Aim 2: For cases like prostate cancer, once an aptamer is determined, it can be utilized in blocking the interaction between tumor cells and stromal cells by binding to and preventing the activation of cell surface receptor tyrosine kinases (RTKs) as shown in Figure 1 (Henderson and Feigelson, 1999). This would in turn alter the expected biological response that would typically occur, hopefully leading to decreased oncogenic symptoms, and thus later applied to other types of cancer besides prostate.
The FGF8b protein is made available by Shawn Piasecki through the Keatinge-Clay lab, with other stock sold through for 0.005mg at $140.00.

  1.  "Evolution of Cancer Treatments: Targeted Therapy." Evolution of Cancer Treatments: Targeted Therapy. American Cancer Society, 8 June 2012. Web. 02 Sept. 2013. <>.
  2. Henderson, Brian E., and Heather S. Feigelson. "Hormonal Carcinogenesis." Oxford Journals 21.3 (1999): 427-33. Oxford Journals. Oxford University Press, 1999. Web. 2 Sept. 2013. <3.>.
  3. White, Robert, and Craig MacArthur. "Assignment OfFGF8to Human Chromosome 10q25–q26: Mutations InFGF8May Be Responsible for Some Types of Acrocephalosyndactyly Linked to This Region." Genomics 30.1 (1995): 109-11. Print.
  4. "Cancer Growth Blockers." : Cancer Research UK : CancerHelp UK. Cancer Research UK, 15 Apr. 2013. Web. 02 Sept. 2013. <>.
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