Abstract

The long-term goal is to elucidate the functions of hamartin and tuberin.
Specific Aims i nclude 1) to identify the germline """"""""first hit"""""""" and somatic """"""""second hit"""""""" mutations in TSC-associated renal cell carcinomas, 2) to identify other somatic genetic events involved in the development of renal cell carcinoma in TSC patients, 3) to define the hamartin-tuberin interaction domain and to determine the effects of naturally occurring mutations on the hamartin-tuberin interaction, and 4) to determine the role of hamartin in cell cycle regulation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK051052-09
Application #
6650265
Study Section
Pathology B Study Section (PTHB)
Program Officer
Rasooly, Rebekah S
Project Start
1995-09-30
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
9
Fiscal Year
2003
Total Cost
$336,000
Indirect Cost

  Institution

Name
Fox Chase Cancer Center
Department
Type
DUNS #
073724262
City
Philadelphia
State
PA
Country
United States
Zip Code
19111

  Publications

Lam, Hilaire C; Nijmeh, Julie; Henske, Elizabeth P (2017) New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex. J Pathol 241:219-225
Li, Chenggang; Zhou, Xiaobo; Sun, Yang et al. (2013) Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis. Am J Respir Cell Mol Biol 49:135-42
Parkhitko, Andrey; Myachina, Faina; Morrison, Tasha A et al. (2011) Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent. Proc Natl Acad Sci U S A 108:12455-60
Karbowniczek, Magdalena; Zitserman, Diana; Khabibullin, Damir et al. (2010) The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous sclerosis complex and Drosophila external sensory organ development. J Clin Invest 120:93-102
Hartman, T R; Nicolas, E; Klein-Szanto, A et al. (2009) The role of the Birt-Hogg-Dubé protein in mTOR activation and renal tumorigenesis. Oncogene 28:1594-604
Karbowniczek, Magdalena; Yu, Jane; Henske, Elizabeth Petri (2003) Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and non-neoplastic vascular structures. Am J Pathol 162:491-500
Duffy, Karen; Al-Saleem, Tahseen; Karbowniczek, Magdalena et al. (2002) Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients. Mod Pathol 15:205-10
Khare, L; Astrinidis, A; Senapedis, W et al. (2002) Expression of wild type and mutant TSC2, but not TSC1, causes an increase in the G1 fraction of the cell cycle in HEK293 cells. J Med Genet 39:676-80