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J Way

Publications and source records attributed to J Way.

29 records · Page 2Linked to original sources
PubMed1988

Multiple mechanisms for transcriptional regulation of the myc gene family in small-cell lung cancer.

The molecular mechanisms reported to regulate the expression of myc family genes are multiple and complex and include gene amplification, transcriptional activation, transcriptional attenuation, and mRNA stability. We have investigated which of these mechanisms are responsible for the extreme variation in myc gene family mRNA levels observed in human small-cell lung cancer cell lines. In addition to gene amplification, a block to nascent mRNA chain elongation, causing attenuation of transcription, is an important regulatory mechanism controlling the steady-state levels of c-myc and L-myc mRNA. The loss of transcriptional attenuation is correlated with overexpression of these two genes in cell lines which do not show gene amplification. Expression of c-myc mRNA appears to be dependent on promoter activity and attenuator function. In contrast, regulation of expression of the N-myc gene does not involve transcriptional attenuation; steady-state mRNA levels are correlated with promoter activity as well as gene amplification. We conclude that transcriptional regulation of each member of the myc gene family is accomplished by a different assortment of complex mechanisms, including gene copy number, promoter activation, and transcriptional attenuation. Interference at multiple points in this complex regulatory process appears to be an important mechanism by which small-cell lung cancer and other human tumors evade growth control.

Carcinoma, Small Cell↗
PubMed1988

Transcriptional activation and DNase I hypersensitive sites are associated with selective expression of the gastrin-releasing peptide gene.

The gastrin-releasing peptide (GRP) is a neuropeptide hormone and growth factor produced normally by neural and neuroendocrine cells, as well as by human small-cell lung cancer (SCLC) tumors and derived cell lines. This study compares the structure of the human prepro-GRP gene in four SCLC cell lines that express variable levels of steady-state GRP mRNA. The regulation of GRP gene expression appears to be at the level of primary transcription based on nuclear run on studies. In the two SCLC cell lines expressing GRP we find a single transcription start site for GRP mRNA, and near this site we find four DNase I hypersensitive sites. These hypersensitive sites are absent in the two cell lines that do not express GRP. The presence of DNase hypersensitive sites in the promoter region of the GRP gene is the structural feature that best correlates with transcriptional activation. These four DNase hypersensitive sites are candidates for cis acting regulatory regions, which may be important in determining the level of transcription of the human prepro GRP gene.

Base Sequence↗
PubMed1988

The rat prepro gastrin releasing peptide gene is transcribed from two initiation sites in the brain.

The gastrin-releasing peptide (GRP) is a gastrointestinal hormone, a neuropeptide, and a growth factor. To study systematically GRP gene expression in embryonic and in adult mammals, we cloned the rat prepro-GRP gene from brain cDNA libraries. Analysis of these cDNA clones along with organ-specific mRNA studies show that there are prepro-GRP transcripts initiating in the brain, but not in the duodenum, from a novel promoter. The latter is located at least four hundred base pairs upstream from a second promoter that is active in both duodenum and in brain. In contrast to human prepro-GRP, there is no alternative processing of the 3'-region of rat brain and duodenum prepro-GRP transcripts; hence, these mRNAs encode a single 147 amino acid prepro-GRP hormone that is homologous to the third isoform of the human prepro-GRP hormone.

Amino Acid Sequence↗
PubMed1987

Continuous intercostal blockade after cardiac surgery.

The provision of analgesia using continuous bilateral intercostal blockade was compared with that provided by conventional i.v. narcotics for the first 48 h after cardiac surgery. The subjective quality of analgesia was significantly superior with the regional technique. However, pulmonary function tests, gas exchange, lung volume, and radiological and clinical evidence of pulmonary complications were not improved. The failure to reduce morbidity and the potential for complications such as pneumothorax, makes it difficult to recommend the regional analgesia technique in this situation.

Cardiac Surgical Procedures↗
PubMed1982

Transposon Tn10: genetic organization, regulation, and insertion specificity.

Transposon Tn10 is a composite element in which two individual insertion sequence (IS)-like sequences cooperate to mediate transposition of the intervening material. The two flanking IS10 elements are not identical; IS10-right is responsible for functions required to promote transposition, and IS10-left is defective in transposition functions. We suggest that the two IS10 elements were originally identical in sequence and have subsequently diverged. IS10-right is compactly organized with structural gene(s), promoters, and sites important for transposition and (presumably) its regulation all closely linked and, in some cases, overlapping. IS10 has a single major coding region that almost certainly encodes an essential transposition function. A pair of opposing promoters flank the start of this coding region. One of these promoters is responsible for expression in vivo of transposon-encoded transposition functions. We propose that the second promoter is involved in modulation of Tn10 transposition. Genetic analysis suggests that transposon-encoded function(s) may be preferentially cis-acting. Insertion of Tn10 into particular preferred target sites is due primarily to the occurrence of a particular six-base pair target DNA sequence. The properties of this sequence suggest that symmetrically disposed subunits of a single protein may be responsible for both recognition and cleavage of target DNA during insertion.

Base Sequence↗