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M W Graber

Publications and source records attributed to M W Graber.

3 recordsLinked to original sources

CaSm: an Sm-like protein that contributes to the transformed state in cancer cells.

A novel gene encoding a protein containing Sm motif-like domains was found to have elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm (for Cancer-associated Sm-like) mRNA is up-regulated in 87.5% (seven of eight) of pancreatic tumor/normal pairs. Similarly, cell lines from cancers originating in liver, ovary, lung, and kidney show increased CaSm expression compared to their normal tissue cognates. CaSm encodes a 133-amino acid open reading frame that contains the two Sm motifs found in the common snRNP proteins, with the greatest homology to the Sm G protein (60% similarity). Two hypothetical proteins from Caenorhabditis elegans and Saccharomyces cerevisiae share even greater similarity (72.8 and 67.7%, respectively), suggesting a broad family of proteins containing Sm motifs. 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. Therefore, CaSm expression appears to be necessary for maintenance of the transformed state.

Amino Acid Sequence

Isolation of differentially expressed genes in carcinoma of the esophagus.

BACKGROUND: The genetic alterations that occur in the transformation of normal esophageal mucosa (NEM) to carcinoma of the esophagus (CAE) are not well understood. Differential display of mRNA is a recently described technique that uses reverse transcription and PCR to compare cDNA from paired normal and malignant tissue to determine whether there is either genetic loss (putative tumor suppressor gene) or overexpression (putative oncogene) in malignant cells. Our goal was to identify some of these genes from patients with CAE. METHODS: Specimens of NEM and corresponding CAE were obtained from patients at endoscopy or surgical resection and immediately snap frozen. Total RNA was isolated, reverse transcribed to cDNA, and PCR amplified with a predefined 10-mer oligonucleotide. The products were displayed on a polyacrylamide gel. Differential bands were isolated and sequenced and/or used as probes for Northern analysis. RESULTS: Application of the differential display method resulted in the isolation of 49 cDNA clones from three patients with CAE. Sequencing of the clones has revealed five unique sequences not previously reported and one that has been identified as histone H3.3. Northern analysis of histone H3.3 has revealed overexpression in four of six CAEs but not the paired NEM. In addition, whereas only 5 of 13 normal human cell lines of various origins overexpressed this gene, 11 of 12 human cancer cell lines (9 of 9 adenocarcinomas) overexpressed it. CONCLUSIONS: Differential display can be used to isolate potential oncogenes and tumor suppressor genes. We have identified five unique sequences and one known gene that may contribute to the development of CAE.

Adenocarcinoma