The perinucleolar compartment (PNC) is a dynamic, irregularly shaped, and electron dense nuclear structure, that is physically associated with the nucleolus. The PNC has been found to be present predominantly in transformed culture cells and several cancer samples examined, but it has been rarely detected in normal fibroblasts and epithelium. Two hnRNPs and several small RNAs have been found enriched in the PNC and the applicant's recent studies suggest that the PNC is involved in transcription and RNA metabolism. The polypyrimidine tract binding protein (PTB), one of the PNC-associated RNA binding proteins, is expressed at a significantly higher level in transformed cells compared to non-transformed cells. The findings suggest that formation of the PNC and increased PTB expression may represent changes of cell and molecular activities in malignantly transformed cells. The applicant's goal is to examine the relationship between PNC formation, PTB expression levels, and human malignancy in vivo, and to evaluate the possibility of using PNCs and PTB concentration as specific tumor markers. In this application, the applicant will seek to accomplish two pilot experimental studies using breast cancer as a model system. In the first aim, the applicant will examine and compare PNC prevalence (the percentage of cells that contain one or more PNCs) in normal, benign, premalignant, and malignant breast tissue samples, and will determine the statistical correlation between PNC prevalence and breast cancers at various stages of progression and degrees of malignancy. In the second aim, the applicant will examine and compare the expression level of the PTB protein in a similar range of breast tissues. Through the proposed studies, the applicant hopes to gain preliminary insights into whether PNC prevalence and PTB concentration could be useful in cancer diagnosis and prognosis.
| Kamath, Rajesh V; Thor, Ann D; Wang, Chen et al. (2005) Perinucleolar compartment prevalence has an independent prognostic value for breast cancer. Cancer Res 65:246-53 |
