Implication of the proliferation and apoptosis associated CSE1L/CAS gene for breast cancer development

The CSEIL/CAS protein (CAS) is a Ran-binding protein with a function as a n uclear transport (export) factor. CSEIL/CAS, similar to Ran and other ran-b inding proteins, plays at the same time an important role in the mitotic sp indle checkpoint, which assures genomic stability during cell division. Thi s checkpoint is frequently disturbed in neoplasms of various origin, includ ing breast, hepatic and colonic tumors. CAS is located on chromosome 20ql3 and amplified in several cell lines, including breast, colon and bladder ca ncer. MEKl phosphorylation is known to be a reason for different CAS locali zation and activity. We evaluated the expression of CAS in 50 benign and ma lignant tumors of the breast by immunohistochemistry. Benign lesions of the breast (n=13) revealed a weak, predominantly cytoplasmatic CAS positivity. In ductal and lobular in situ carcinomas (n=17), 70-90% of the tumor cells were positive for anti-CAS staining which was predominantly cytoplasmatic. In invasive ductal and lobular carcinomas (n=20), 70-90% of the tumor cell s stained positive with anti-CAS in a predominantly nuclear pattern. Differ ent localization of CAS might affect its role not only for chromosome segre gation, proliferation and apoptosis, but also its function in nuclear trans port of proteins like retinoblastoma-gene-product, p53 and BRCAl. A differe nt regulation in this checkpoint might contribute to the invasive potential in malignant carcinomas of the breast. Alteration of CAS-activity, possibl y via MEKl-inhibition, might therefore be a possible option for breast canc er therapy.