Selection of an Aptamer Against FGF8b for Breast Cancer and prostate Cancer Treatment

Shuhui Wan

FGF8, the fibroblast growth factor (1), a protein that is inducible by androgen in breast cancer cells, is involved in many hormone related cancers, such as breast cancer and prostate cancer (2,3). More than 67% of breast cancer patients and over 93% of prostate cancer patients showed expression of FGF8 (3). And the breast cancer tissues were show to express much higher level of FGF8 mRNA than the non-malignant tissues (4). One specific isoform, FGF8b, was proved to induce progression of prostate cancer (5).

Because of FGF8b’s significant involvement with tumor growth, it was thought that by inhibiting the activities of this growth protein the tumor growth could also be greatly suppressed. One promising way of doing this would be finding an aptamer, a RNA ligand that binds to specific targets, for FGF8b. The apatamer for FGF8b may bind to it and inhibiting the protein from functioning in promoting tumor growth. In other words, the aptamer could be used for therapeutic purposes to treat breast cancer and prostate cancer in future.

Specific aim #1: find an aptamer that binds specifically to FGF8b.

Specific aim #2: modify the aptamer to be used for therapeutic purposes.

Specific aim #3: use the modified aptamer as a drug for breast and prostate cancer treatment.

Figure 1: structure of FGF8b(1)..

FGF-8b is prepared by Shawn Piasecki and available in lab.


...so the references are not showing up, here's the PDF version file:
https://docs.google.com/file/d/0B38waIP26ToBdDRBX1lLMXItQU0/edit?usp=sharing

progress report 1
https://docs.google.com/file/d/0B38waIP26ToBZUpkX3N1a1pvdzg/edit?usp=sharing

progress report 2
https://drive.google.com/file/d/0B38waIP26ToBQUZWSjFCRU83NUE/edit?usp=sharing

Final report

References:

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(1) Goetz R, Mohammadi M, Exploring mechanisms of FGF signalling through the lens of structural biology. Nat Rev Mol Cell Biol. 2013 Mar;

(2) Payson RA, Wu J, Liu Y, Chiu IM. The human FGF-8 gene localizes on chromosome 10q24 and is subjected to induction by androgen in breast cancer cells. Oncogene. 1996 Jul 4;13(1):47-53.

(3) Mattila MM, Ruohola JK, Valve EM, Tasanen MJ, Seppänen JA, Härkönen PL. FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells. Oncogene. 2001 May 17;20(22):2791-804.

(4) Tanaka A, Furuya A, Yamasaki M, Hanai N, Kuriki K, Kamiakito T, Kobayashi Y, Yoshida H, Koike M, Fukayama M. “High frequency of fibroblast growth factor (FGF) 8 expression in clinical prostate cancers and breast tissues, immunohistochemically demonstrated by a newly established neutralizing monoclonal antibody against FGF 8.” Cancer Res. 1998 May 15;58(10):2053-6.

(5)Marsh SK, Bansal GS, Zammit C, Barnard R, Coope R, Roberts-Clarke D, Gomm JJ, Coombes RC, Johnston CL. Increased expression of fibroblast growth factor 8 in human breast cancer. Oncogene. 1999 Jan 28;18(4):1053-60.

(6)Valta MP, Tuomela J, Vuorikoski H, Loponen N, Väänänen RM, Pettersson K, Väänänen HK, Härkönen PL. FGF-8b induces growth and rich vascularization in an orthotopic PC-3 model of prostate cancer. J Cell Biochem. 2009 Jul 1;107(4):769-84. doi: 10.1002/jcb.22175.

(7) Gwen Stovall, PowerPoint - “Bead Based RNA Selection, Lecture 09”, slide 21, 2013