The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.

Animals↗

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Carcinogenicity of TCDD in laboratory animals: implications for risk assessment.

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Animals↗

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Elevated 80K-H protein in breast cancer: a role for FGF-1 stimulation of 80K-H.

An increase in fibroblast growth factor-1 (FGF-1) is established as part of the cause of several important cancers including breast cancer, but the mechanisms by which it induces malignant behavior are not known. We now report that the protein 80K-H, a substrate for PKC, appears to be part of this mechanism and that it is increased in breast cancer and localizes to the nucleus as part of the mechanism. Our conclusion is based on an examination of a total of 58 biopsy specimens from human breast cancer patients for the presence of relationships between the 80K-H protein and the following: fibroblast growth factor receptor-1 (FGFR-1), tumor grade, microvessel counts (MVC), estrogen receptor (ER) and progesterone receptor (PgR) status. Based on histological grading and immunohistochemical (IHC) assays, we found strong direct relationships between 80K-H and FGFR-1 (r = 0.49, p = 0.003) and tumor grade (r = 0.42, p = 0.006). A trend for a direct relationship was observed with PgR (r=0.27, p=0.087). Notably, 80K-H immunostaining was largely limited to the epithelial cells of the mammary ducts. Subsequently, we studied the effects of FGF-1 on 80K-H in cultured human mammary carcinoma epithelial cells in order to establish a more direct relationship between these two molecules. We observed that FGF-1 treatment of MCF-7 cells stimulated translocation of 80K-H protein to the cell nucleus, as demonstrated by subcellular fractionation studies. Maximal intranuclear 80K-H was observed approximately 30 minutes following FGF-1 treatment. In addition, FGF-1 treatment of MCF-7 cells increased growth and invasion of MCF-7 cells, as demonstrated by cell proliferation and a modified Boyden chamber assay, respectively. Further support for 80K-H nuclearization was provided by the immunostaining of human breast cancer specimens and computer-assisted identification of a putative nuclear localization signal (NLS) near the amino terminus of 80K-H protein structure. These data support the existence of a previously unrecognized FGF-1/80K-H nuclear pathway in progression of human breast cancer and suggest that 80K-H may be useful for the assessment of breast tumor progression.

Active Transport, Cell Nucleus↗

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