The PTEN gene encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase pathway and is inactivated in a wide variety of malignant neoplasms. High rates of loss of heterozygosity are observed at the 10q23.3 region containing the human PTEN gene in prostate cancer and other human malignancies, but the demonstrated rate of biallelic inactivation of the PTEN gene by mutation or homozygous deletion is significantly lower than the rate of loss of heterozygosity. The transgenic adenocarcinoma of mouse prostate model is a well characterized animal model of prostate cancer. Analysis of prostate cancer progression in transgenic adenocarcinoma of mouse prostate mice bred to Pten ؉/؊ heterozygous mice, coupled with analysis of the Pten gene and protein in the resulting tumors, reveals that haploinsufficiency of the Pten gene promotes the progression of prostate cancer in this model system. This observation provides a potential explanation for the discordance in rates of loss of heterozygosity at 10q23 and biallelic PTEN inactivation observed in prostate cancer and many human malignancies.T he PTEN tumor suppressor gene (also known as MMAC-1) encodes a phosphatase and is inactivated in a wide variety of human malignant neoplasms, including gliomas, melanomas, and carcinomas of the endometrium, kidney, breast, lung, upper respiratory tract, and prostate (1-4). The tumor suppressor activity of PTEN is thought to be primarily due to its ability to dephosphorylate phosphatidylinositol 3,4,5-phosphate at the 3-position and negatively regulate the activity of the phosphatidylinositol 3-kinase pathway (5, 6). A variety of biological effects have been attributed to loss of PTEN activity that are relevant to its role as a tumor suppressor gene, including enhanced cell proliferation (6), decreased apoptosis (5, 6), and increased tumor angiogenesis (7,8). The PTEN gene is also mutated in Cowden syndrome (9), a hereditary neoplastic syndrome characterized by an increased rate of thyroid cancer and breast cancer in affected females. Thus, the PTEN gene is an important tumor suppressor with a wide range of biological activities relevant to tumor progression.The PTEN tumor suppressor gene maps to human chromosome 10q23.3, and this region shows high rates of loss of heterozygosity (LOH) in a variety of human malignancies. Such LOH is usually due to the loss of relatively large areas of one copy of chromosome 10. It is generally believed that in the presence of such LOH the tumor suppressor gene present on the retained chromosome is inactivated by smaller deletions, resulting in homozygous deletion or by mutation. However, for the PTEN gene, the rate of LOH at 10q23.3 is often much higher than the apparent rate of inactivation of the retained PTEN allele. For example, LOH at 10q23.3 has been detected in 15-49% of clinically localized human prostate cancers, whereas mutation or homozygous deletion of the PTEN gene is detected in less than 10% of these same cases (4, 10-15). Similarly, LOH at 10q23 is present in m...

Detailed measurements of crystal outlines and fabrics have been performed on 35 000 crystals in fifteen 10 × 20 cm2 vertical thin sections from the North Greenland Icecore Project (NorthGRIP) ice core, evenly distributed in the depth interval 115–880m. The crystals exhibit important changes over this period. As the ice gets older the mean crystal area increases towards a constant value, the shape of the crystals becomes increasingly irregular, and the area distribution of crystals develops from a single log-normal distribution into a bimodal lognormal distribution. The c-axis fabric of the ice shows a smooth development of an increasingly stronger vertical fabric with depth, and the formation of a weak vertical girdle. Already in the younger samples the fabric is rather strongly oriented towards vertical. The fabric and the area of individual crystals are found not to correlate. A simple model, which takes into account the vertical strain of the ice, is applied in an attempt to determine the crystal growth rate at NorthGRIP.

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Tumor necrosis factor‐α is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor‐α. Treatment with tumor necrosis factor‐α for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor‐α treatment increased the expression of the cytokine interleukin‐6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor‐α, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor‐α induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor‐α. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor‐α treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.