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A putative tumor suppressor locus on the short arm of human chromosome 9 has been localized to a region of less than 40 kilobases by means of homozygous deletions in melanoma cell lines. This region contained a gene, Multiple Tumor Suppressor 1 (MTS1), that encodes a previously identified inhibitor (p16) of cyclin-dependent kinase 4. MTS1 was homozygously(More)
K+ channels are known through electrophysiology and pharmacology to be an exceptionally diverse group of channels. Molecular studies of the Shaker (Sh) locus in Drosophila have provided the first glimpse of K+ channel structure. The sequences of several Sh cDNA clones have been reported; none are identical. We have isolated and examined 18 additional Sh(More)
The Drosophila Shaker (Sh) gene appears to encode a type of voltage-sensitive potassium (K+) channel called the A channel. We have isolated Sh as part of a 350 kb chromosomal walk. The region around Sh contains four identified transcription units. We find that Sh corresponds to a very large transcription unit encompassing a total of about 95 kb of genomic(More)
A locus for familial melanoma, MLM, has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16INK4 (CDKN2) MTS1. This gene is homozygously deleted from many tumour cell lines including melanomas, suggesting that CDKN2 is a good candidate for MLM. We have analysed CDKN2 coding sequences in pedigrees(More)
The p16 gene (P16, MTS1, CDKN2) encodes a negative regulator of the cell cycle. Molecular genetic techniques have been used to explore the role of p16 in normal development and cancer. Two transcripts derived from the p16 gene with distinct protein coding potentials are described. The previously undescribed transcript form has the same exons 2 and 3 as the(More)
The p16 gene (CDKN2) which is localized on chromosome 9p21, is deleted in a significant number of sporadic cancers. Moreover, germline mutations identified in some melanoma-prone kindreds last year suggested that CDKN2 is identical to the 9p21-linked melanoma susceptibility gene (MLM); however, failure to identify p16 mutations in all melanoma kindreds(More)
The P15 gene (MTS2) encodes a cyclin-dependent kinase (CDK) inhibitor with considerable sequence identity and biochemical similarity to the CDK inhibitor p16. It is closely linked to the P16 gene (MTS1) and is homozygously deleted in many tumor cell lines. These features suggest that p15 may be a tumor suppressor. We have determined the genomic structure of(More)
The beta-catenin pathway is involved in growth, differentiation and tumor formation. Suppression of pathway activity by expressed inhibitors can cause growth arrest or apoptosis in certain colon carcinoma lines. We compare the effects of 2 pathway inhibitors, a VE-cadherin cytoplasmic domain fragment (Cad5CD) and a truncated, dominant-negative Tcf4 (TcfDN),(More)
Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk(More)
Oncology, as a therapeutic area, is characterized by a desperate medical need for new drugs; the use of drugs that kill cells and which are consequently often toxic; and rates of failure in expensive Phase III trials that eclipse many other disease areas. The poor performance of most investigational cancer drugs implies that the standard preclinical disease(More)