ABSTRACT
Approximately 90% of human ovarian tumors result from transformation of ovarian surface epithelial cells. It has been hypothesized that repeated destruction of the epithelial cells during ovulation, followed by proliferation and migration of epithelial cells to restore the ovarian surface, renders these cells susceptible to mutagenic events. One of the proteins found to promote ovarian surface epithelial cell survival and proliferation was the transcription factor, cAMP response element-binding protein (CREB). Thus, the objective of this study was to determine whether CREB was also highly expressed in tumor cells originating from the ovarian epithelium. Using an ovarian cancer tissue array, it was observed that approximately 54% of the epithelial-derived human ovarian tumors displayed moderate or high levels of CREB immunostaining, while none of the normal ovarian samples did. Comparison of CREB levels in a human ovarian tumor cell line to those of a normal ovarian epithelial cell line revealed elevated levels of CREB and phosphorylated CREB in the ovarian tumor cells. To determine whether CREB regulated proliferation and/or apoptosis in the ovarian tumor cell line, CREB expression was suppressed using RNA interference. Decreased CREB expression significantly reduced ovarian tumor cell proliferation, while there was no effect on apoptosis in these cells. Finally, we showed that CREB is highly expressed in an in vivo murine model of ovarian tumorigenesis. Therefore, CREB is frequently overexpressed in ovarian cancer where it appears to promote cell proliferation.
Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Cyclic AMP Response Element-Binding Protein/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Adenocarcinoma/genetics , Animals , Cell Line, Tumor , Cell Proliferation , Cyclic AMP Response Element-Binding Protein/genetics , Disease Models, Animal , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Neoplasm Staging , Ovarian Neoplasms/genetics , Phosphorylation , Tissue Array AnalysisABSTRACT
This study provides an accurate, anatomical description of the rabbit's lumbosacral spinal cord. Following humane euthanasia, 64 rabbits were radiographed and dissected. The number of thoracic (T) and lumbar (L) vertebrae was 12T/7L in 43.8%, 13T/6L in 32.8%, and 13T/7L in 23.4% in the 64 rabbits studied. The 13th ribs were rudimentary, asymmetric, or both in 15 animals. The spinal cord terminated within the second sacral vertebra (S2) in 79.3%, within the first sacral vertebra (S1) in 19.0%, and within the third sacral vertebra (S3) in 1.7% of the sample. Spinal nerve contributions to the femoral, obturator, sciatic, and pudendal nerves were determined. Formulas to predict the termination of the cord relative to the vertebral column were established. Age, weight, sex, and method of preparation did not show a significant correlation with the length of the spinal cord.
