The proposed studies will evaluate the potential for a unique nuclear structure, the perinucleolar compartment (PNC), to be used as an immunocytochemical marker in the diagnosis of cancer. The work will also purify and characterize the structural components of the PNC. The association between the PNC and carcinogenesis will also be analyzed. Preliminary studies have shown that he PNC is present in many human cancer cells lines, but is mostly absent from normal diploid cells. To test the correlation between the PNC and human cancer, PNC prevalence (the percentage of cells that contain a PNC) in a large number of cancer samples and their normal counterparts will be examined and compared. An antibody specifically recognizing a polypyrimidine binding protein (PTB), the only protein component identified in the PNC thus far, will be sued as a probe to detect the PNC. If a significant correlation between PNC prevalence and cancers of various clinical stages and pathological grades can be established, PNC prevalence may provide an additional marker in the diagnosis of the disease. In addition, the structural and functional characteristics of the PNC will be investigated using both molecular and cellular approaches. Additional components in the PNC will be identified, cloned, and the functional interactions among them will be analyzed. The role of the PNC in the process of carcinogenesis will also be examined. These proposed studies will inevitably further our understanding in the relationship between the PNC and cancers, as well as the structural and functional characteristics of the PNC. These work will also represent a link between the basic research and clinical applications.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA074988-03
Application #
2748948
Study Section
Subcommittee G - Education (NCI)
Program Officer
Springfield, Sanya A
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Anatomy/Cell Biology
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Chen, Danyang; Hinkley, Craig S; Henry, R William et al. (2002) TBP dynamics in living human cells: constitutive association of TBP with mitotic chromosomes. Mol Biol Cell 13:276-84
Pendergrast, P Shannon; Wang, Chen; Hernandez, Nouria et al. (2002) FBI-1 can stimulate HIV-1 Tat activity and is targeted to a novel subnuclear domain that includes the Tat-P-TEFb-containing nuclear speckles. Mol Biol Cell 13:915-29
Kamath, R V; Leary, D J; Huang, S (2001) Nucleocytoplasmic shuttling of polypyrimidine tract-binding protein is uncoupled from RNA export. Mol Biol Cell 12:3808-20
Chen, D; Huang, S (2001) Nucleolar components involved in ribosome biogenesis cycle between the nucleolus and nucleoplasm in interphase cells. J Cell Biol 153:169-76
Dousset, T; Wang, C; Verheggen, C et al. (2000) Initiation of nucleolar assembly is independent of RNA polymerase I transcription. Mol Biol Cell 11:2705-17
Huang, S; Deerinck, T J; Ellisman, M H et al. (1998) The perinucleolar compartment and transcription. J Cell Biol 143:35-47