Accession Number : ADA560532


Title :   Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer


Descriptive Note : Annual summary rept. 1 Mar 2011-29 Feb 2012


Corporate Author : M D ANDERSON CANCER CENTER HOUSTON TX


Personal Author(s) : Jain, Shalini


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a560532.pdf


Report Date : Mar 2012


Pagination or Media Count : 19


Abstract : Over the last 50 years, the number of cancer related deaths has decreased by only 2%. To achieve reduced breast cancer mortality, it is critical to develop early detection and intervention of breast cancer development at early stages of cancer initiation. This requires better understanding of the critical molecular alterations driving early lesions (atypia) to progress to cancer and developing new interventions based on the observed alterations. Although tamoxifen (Tam) has shown efficacy in prevention of ER+ breast cancers, but they remain ineffective for ER- cancer, therefore new agents are needed to prevent ER- breast cancer. More than 60% of total breast cancer patients are ER-, PRand HER-2+. However, there are approximately 15% of all types of breast cancer in women who do not express ER , PR, and HER-2 (5). ER- breast cancer is associated with either HER2-overexpressing (HER2+) luminal-type, or EGFR-overexpressing (EGFR+) basal-type, and other signaling events dysregulating ER pathway. Recently, the crosstalk between the ligand bound ER and the tyrosine kinase Src has been reported in breast cancer cells, which appears to enhance the proteasomal degradation of ER . In this study, it has been shown that transfection of Src into MCF-7 cells resulted in decreased levels of ER protein, but not mRNA. Moreover, they showed that it may be in a subset of ER - breast cancer with activated Src may lead to the ER - phenotype. Clinical-pathologic studies have shown elevated c-Src protein levels and/or activity in about 70% of primary human breast and other epithelial tumors, often associated with ErbB2 or EGFR overexpression. Studies from our lab have shown that activation of ErbB2 and downstream signaling pathways can lead to increased Src protein synthesis and decreased Src protein degradation leading to Src up-regulation and activation, which play critical roles in ErbB2-mediated breast cancer invasion and metastasis. Therefore we hypothesized that Src may play impor


Descriptors :   *BREAST CANCER , *DEATH , *ESTROGENS , BIOSYNTHESIS , CELLS(BIOLOGY) , DEGRADATION , DETECTION , EPITHELIUM , MAMMARY GLANDS , MOLECULES , MORTALITY RATE , NEOPLASMS , PATIENTS , PHOSPHORUS TRANSFERASES , PREVENTIVE MEDICINE , PROTEINS , RECEPTOR SITES(PHYSIOLOGY) , RIBONUCLEIC ACIDS , TYROSINE , WOMEN


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE