The United States of America as Represented by the Department of Health

Musc Foundation for Research Development

Other

The United States of America, as Represented by the Secretary, Department of Health and Human Services

The United States of America as Represented by the Secretary of

Takis S Papas

Clifford W Schweinfest

James A Lautenberger

Flossie Wong-Staal

Kenneth Samuel

Narayan K Bhat

Hiroaki Suzuki

John N Vournakis

Dennis K Watson

Paul L Baron

Arun K Seth

The present invention relates to a novel gene, CaSm, that is highly expressed in cancer tissues and cell lines, especially pancreatic cancer. The full length cDNA of CaSm encodes a protein of 133 amino acids. CaSm contains the two Sm motifs found in the common snRNP proteins, with the greatest homology to the Sm G protein (60% similarity). The present invention further encompasses CaSm peptides, fusion proteins, host cell expression systems, antibodies to CaSm, antisense CaSM molecules, and compounds that modulate CaSm gene expression or CaSm activity. Antisense CaSm RNA is able to alter the transformed phenotype of pancreatic cancer cells by reducing their ability to form large colonies in soft agar when compared to untransfected cells. The present invention also encompasses methods for disease diagnosis, drug screening and the treatment of cancer.

Methods and compositions for diagnosis and treatment of cancer

The present invention relates to a novel gene, Di12, that is differentially expressed as a 1.35 kb RNA in breast cancer tissues and cell lines, and in several normal tissues. The full length cDNA encodes a protein of 339 amino acids. Antibodies to the gene product were developed to investigate the expression of Di12 in breast cancer cell-lines and tumors. The Di12 protein was found in tissue sections of infiltrating ductal carcinomas (IDCs), but not in benign or normal breast specimens. Di12 wag also present in IDC-breast cancer patient sera, and its expression level increased markedly if IDC was accompanied by lymph node or distal metastases. As IDC constitutes &tilde;70% of breast cancers seen clinically, the level of Di12 expression is useful for diseases diagnosis predicting disease progression and monitoring a therapeutic treatment.

Methods and compositions for diagnosis and treatment of breast cancer

A new down-regulated gene called DRA, for down regulated in adenoma, maps to chromosome 7 and is believed to encode a tumor suppressor. The DRA gene encodes a highly hydrophobic protein with charged clusters located primarily in the carboxyl terminus. Additionally, the expression of the mRNA product appears to be strictly limited to the mucosa of normal colon and it is down-regulated early in colon tumorigenesis. Absence of the DRA polypeptide in tissue that usually expresses it can be used as an indicator of tissue abnormality. The DRA gene and cDNA may also have therapeutic capabilities as well.

Methods for evaluating colon tissue for expression of the DRA (down regulated in adenoma) gene

Colon mucosa gene having down-regulated expression in colon adenumas and

The present invention relates, in general, to methods for reducing cell tumorigenicity. More particularly, the present invention provides a method for reducing cell tumorigenicity comprising transfecting a tumor cell with an ETS1 gene, the tumor cell not endogenously expressing the ETS1 gene. In addition, the present invention provides a method for reducing cell tumorigenicity comprising contacting a tumor cell with a peptide expressed by an ETS1 gene, the tumor cell not endogenously expressing the ETS1 gene. The methods of the present invention are particularly useful for reducing tumorigenicity in epithelial tumor cells.

ETS1 gene: a human tumor suppressor gene

Antigenic proteins may be expressed in bacteria by use of vectors having inserted therein DNA fragments from an envelope gene. The DNA fragments employed in the example are coding sequences found in the HTLV-I envelope gene. The bacteria used was E. coli. The antigenic proteins are useful in identifying antibodies to the organisms from which the DNA fragments were originally obtained.

Productive of human T-cell leukemia (lymphotropic) retrovirus (HTLV-1)

The present invention relates, in general, to methods for reducing cell tumorigenicity. More particularly, the present invention provides a method for reducing cell tumorigenicity comprising transfecting a tumor cell with an ETS1 gene, the tumor cell not endogenously expressing the ETS1 gene. In addition, the present invention provides a method for reducing cell tumorigenicity comprising contacting a tumor cell with a peptide expressed by an ETS1 gene, the tumor cell not endogenously expressing the ETSI gene. The methods of the present invention are particularly useful for reducing tumorigenicity in epithelial tumor cells.

Colon mucosa gene having down regulated expression in colon adenomas and

Production of human T-cell leukemia (lymphotropic) retrovirus (HTLV-I)

The plasmid of this invention contains the cII translation initiation site and a P.sub.L promoter--both are very efficient, producing large amounts of cII protein. This plasmid contains a unique ClaI restriction site in the aminoterminal portion of the cII gene suitable for insertion of foreign genes. This plasmid is an improvement over other plasmids because the inserted genes are subject to the same transcriptional and translational characteristics of the cII gene; this plasmid, therefore, produces large amounts of the protein coded by the exogenous gene.

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Potomac, MD, United States of America

Takis S Papas