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UOK 257, the First BHD Tumor Cell Line, and UOK257-2 Wild Type FLCN-restored Renal Cell Line as In Vitro and In Vivo Models of E

Posted Jun 06 2010 5:00pm

Description of Invention:
Scientists at the National Institutes of Health (NIH) have developed a novel renal cell carcinoma (RCC) cell line designated UOK257, which was derived from the surgical kidney tissue of a patient with hereditary Birt-Hogg-Dubé (BHD) syndrome and companion cell line UOK257-2 in which FLCN expression has been restored by lentivirus infection. These cell lines harbors a germline mutation of FLCN gene (alias BHD) and displays loss of heterozygosity, can grow as xenograft in nude mice. Patients affected with BHD develop skin papules (fibrofolliculomas), lung cysts, spontaneous pneumothorax and an increased risk for bilateral multifocal renal tumors. Loss of both copies of the FLCN gene has been documented in BHD renal tumors; however, the molecular mechanisms by which inactivation of the encoded protein, folliculin, leads to the BHD phenotype are currently unknown. They have developed an important research tool for in vitro folliculin functional studies. The companion cell line will be extremely useful for comparative biochemical analyses of cell culture systems in which the FLCN gene is either expressed or inactivated, including identification of renal tumor biomarkers, alteration of biochemical pathways resulting from loss of FLCN function, tumorigenicity of FLCN null versus FLCN restored cells, preclinical therapeutic drug testing in xenograft animal models produced from injection of these cell lines, etc. UOK 257 and UOK257-2 are thus useful cell models for studying the underlying molecular derangements associated with mTOR pathways and other biogenesis pathways in human kidney cancer and for evaluating novel therapeutic approaches for this disease. UOK257 is also one of the 40-member renal cancer cell lines in the Tumor Cell Line Repository of the Urologic Oncology Branch (UOB), National Cancer Institute (NCI).

  • In vitro and in vivo cell model for BHD cancer syndrome. Research tool for investigating the underlying molecular mechanisms contributing to advanced BHD, including the identification of new BHD tumor antigens for immunotherapy.
  • Research tool for studying genes transcription status of genes involved in BHD to reveal the genetic processes occurring in BHD tissues that may contribute to advanced disease.
  • Positive control cell line for FLCN gene expression and function studies, including cytogenetics, gene mutation research, and examination abnormalities of interaction with other proteins that may contribute to BHD.
  • Research tools for testing the activity of potential anti-cancer drugs against BHD, a disease which has no effective treatment options; tool for searching tumor markers for diagnosis, prognosis and drug resistance.
  • Therapeutic drug testing for targeting BHD renal tumors, possible starting material for developing a cancer vaccine against BHD.

  • Cell line is derived from a BHD patient: These cell lines are anticipated to retain many features of primary BHD samples and novel BHD antigens identified from this cell line are likely to correlate with antigens expressed on human BHD type of RCC tumors. Studies performed using these cell lines may have a direct correlation to the initiation, progression, treatment, and prevention of BHD type of RCC in humans.
  • Molecular and genetic features are well characterized: This cell line is part of NCI Urologic Oncology Branch's Tumor Cell Line Repository. The inventor has elucidated many physical characteristics of the cell lines, including chromosomal attributes and valuable studies on functions of BHD gene, their data suggest that FLCN, mutated in the BHD syndrome, and its novel interacting partner, folliculin-interacting protein (FNIP1), may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways.

W Marston Linehan (NCI)

Patent Status:
HHS, Reference No. E-131-2010/0

Research Tool -- patent protection is not being pursued for this technology

Relevant Publication:
  1. Yang Y, Padilla-Nash HM, Vira MA, Abu-Asab MS, Val D, Worrell R, Tsokos M, Merino MJ, Pavlovich CP, Ried T, Linehan WM, Vocke CD. The UOK 257 cell line: a novel model for studies of the human Birt-Hogg-Dubé gene pathway. Cancer Genet Cytogenet. 2008 Jan 15;180(2):100-109. [ PubMed: 18206534 ]
  2. Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF 3rd, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR Jr, Linehan WM, Schmidt LS, Zbar B. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci USA. 2006 Oct 17;103(42):15552-15557. [ PubMed: 17028174 ]

Licensing Status:
Available for licensing under a Biological Materials License Agreement.

Collaborative Research Opportunity:
The Center for Cancer Research, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize kidney cancer tumor cell lines as described in above abstract through MTA, CRADAs, CTAs, BML, etc.:
  • For laboratory interests on the basis of metazoan tumor cell survival, including growth factor-regulated nutrient uptake; glucose or glutamine metabolism and epigenetic gene control; tumor cell bioenergetics and cell growth through AMPK and mTOR signaling pathways.
  • In vitro and in vivo cell model for BHD cancer syndrome. It is voluble research tool for laboratory interested in identification of new BHD tumor antigens for immunotherapy.
  • These paired cell lines for FLCN gene expression and function studies, including gene therapy, cytogenetics, gene mutation research, and examination abnormalities of interaction with other proteins that may contribute to BHD.
  • The excellent in vivo model for preclinical xenograft imaging, including stable transfection. Cells could be labeled with reagents for PET, Luciferase, Fluorescent, for transgenic mice, optical molecular imaging, etc., and provides useful platform for preclinical drug evaluations.
Please contact John Hewes, Ph.D. at 301-435-3121 or for more information.

Devices/Instrumentation - Research Tools and Materials
Cancer - Research Materials
Research Materials

For Additional Information Please Contact:
Betty Tong Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-594-6565
Fax: 301-402-0220

Ref No: 2111

Updated: 06/2010

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