Cancer is the second leading cause of death in the U.S. This year, 212,600 new cases of breast cancer and 61,000 cases of lymphoma are expected, killing nearly 20% of women and 40%, respectively. Development of new diagnostic markers is of keen interest and would improve early dectection in cancer patients and help physicians in clinical decision-making. Cancer progression is often attributed to the misregulation of the cell cycle. The cell cycle is regulated by the interaction of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CKIs). p27, a CKI, regulates the G1/S phase transition of the cell cycle and plays a critical role in controlling the cell cycle. Abnormally low levels of the p27 protein are frequently found in 50% of breast cancers. Cytoplasmic mislocation of p27 and subsequent inactivation occurs in 40% of breast tumors, suggesting the importance of this cell-cycle regulator. JAB1 (Jun activation domain-binding protein) was recently found to regulate mammalian checkpoint through inactivation of p27 by facilitating relocation of p27 from the nucleus to the cytoplasm, accelerating its degradation. A clinical study of 53 women with invasive breast carcinoma showed that JAB1 protein levels were inversely correlated with p27. The same inverse correlation of JAB1 and p27 were observed in Non-Hodgkins lymphoma (NHL). Clinical outcomes indicate that JAB1 may be a marker for breast cancer and NHL. Further studies are needed to validate these potential uses of JAB1.
The specific aims proposed in this project are: (1) Determine whether JAB1 and p27 protein expression can be used as a biomarker in breast carcinoma and NHL and Hodking'disease; and (2) Examine whether the Jab1 gene is amplified. We will use tissue microarrays, immunohistochemical and statistical methods to analyze the expression of p27 and JAB1 in archival sections from 250 patients' breast cancer tissue samples. Development of new prognosis/diagnostic markers for breast cancer and lymphoma would be invaluable. ? ?
| Atsaves, V; Zhang, R; Ruder, D et al. (2015) Constitutive control of AKT1 gene expression by JUNB/CJUN in ALK+ anaplastic large-cell lymphoma: a novel crosstalk mechanism. Leukemia 29:2162-72 |
| Vivas-Mejia, Pablo; Benito, Juliana Maria; Fernandez, Ariel et al. (2010) c-Jun-NH2-kinase-1 inhibition leads to antitumor activity in ovarian cancer. Clin Cancer Res 16:184-94 |
| Kouvaraki, Maria A; Korapati, Anita L; Rassidakis, George Z et al. (2006) Potential role of Jun activation domain-binding protein 1 as a negative regulator of p27kip1 in pancreatic adenocarcinoma. Cancer Res 66:8581-9 |
