Abstract 1679: Increased expression of hCAS/CSE1L in colorectal cancer: Correlation with tumor progression

Abstract

Abstract Introduction. The human cellular apoptosis susceptibility (hCAS) gene product has been shown to be involved in cellular proliferation, apoptosis, invasion and metastasis. CSE1 is a yeast gene with high homology to hCAS (CSE1-like or CSE1L) which has been shown to be involved in chromosome segregation during mitosis. hCAS has also been shown to be a key player in cytoplasm-to-nuclear transport by shuttling importin-alpha from the nucleus back out into the cytoplasm. We hypothesized that the expression of hCAS may be altered during the progression of human colorectal cancer (CRC). Methods. In order to examine hCAS at the gene expression level, we surveyed three different datasets from studies in which Affymetrix U133+gene chips had been performed on patients with CRC, as well as patients with adenomas and normal individuals. We examined relative gene expression levels for 3 probe sets on the U133+ gene chip that closely align to the refseq for the hCAS gene. hCAS protein expression level was semiquantitatively measured using immunohistochemistry (IHC) and the tissue microarray (TMA) technique. A CRC TMA had been previously created at the Moffitt Cancer Center using resection specimens of primary CRC of different stages, and inclusive of adenomas and normal tissues samples from the same patients. Results. hCAS gene expression was increased in all adenoma and CRC samples tested by microarray, compared to histologically normal colonic mucosa. However, the difference in hCAS mRNA levels between adenoma and CRC samples was not statistically different. No correlation was found between hCAS and cancer stage, grade, vascular invasion, sex and/or age. Interestingly, in the invasive CRCs, intense hCAS proteins expression was localized to both nucleus and cytoplasm. Conversely, early stage lesions showed predominantly cytoplasmic hCAS staining. Conclusions. Our results demonstrate that hCAS protein is expressed early and across all stages of CRC development. Because of its early expression hCAS may represent a marker for early detection of CRC. In addition, because of its involvement in a variety of important cellular processes, this gene product might represent a new potential target for prevention and treatment of CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1679. doi:10.1158/1538-7445.AM2011-1679