Mouse and human retinoic acid receptor β2 promoters:Sequence comparison and localization of retinoic acid responsiveness

The retinoic acid receptor β (RARβ gene is a member of the family of retinoic acid/thyroid hormone receptor genes, encoding retinoic acid-inducible transcription factors. To study regulation of the RARβ gene, genomic clones containing the mouse and human retinoic acid receptor β2 (RARβ2) promoters were isolated and approximately 1.5 kb of upstream and downstream sequences relative to the transcriptional start site were completely sequenced. Both the mouse and human RARβ2 promoters are highly homologous around the transcription initiation site, with perfect conservation of the TATA box and retinoic acid responsive element (RARE). Promoter activation studies in P19 EC cells show, that the RARE in both the human and mouse promoters confers RA-responsiveness to the RARβ2 promoter. However, sequences located immediately upstream of the RARE also confer RA-inducibility to both the mouse and human RARβ2 gene promoters. This region contains conserved consensus sequences for a TPA-responsive element (TRE) and cAMP-responsive element (CRE), suggesting that in addition to regulation by RA receptors other transcription factors regulate RAR/β2 expression in EC cells. Furthermore, the availability of the mouse RARβ2 promoter should facilitate studies for transgene expression and gene targeting experiments in embryonic stem cells.</p

Mouse and human retinoic acid receptor β2 promoters:Sequence comparison and localization of retinoic acid responsiveness

The retinoic acid receptor β (RARβ gene is a member of the family of retinoic acid/thyroid hormone receptor genes, encoding retinoic acid-inducible transcription factors. To study regulation of the RARβ gene, genomic clones containing the mouse and human retinoic acid receptor β2 (RARβ2) promoters were isolated and approximately 1.5 kb of upstream and downstream sequences relative to the transcriptional start site were completely sequenced. Both the mouse and human RARβ2 promoters are highly homologous around the transcription initiation site, with perfect conservation of the TATA box and retinoic acid responsive element (RARE). Promoter activation studies in P19 EC cells show, that the RARE in both the human and mouse promoters confers RA-responsiveness to the RARβ2 promoter. However, sequences located immediately upstream of the RARE also confer RA-inducibility to both the mouse and human RARβ2 gene promoters. This region contains conserved consensus sequences for a TPA-responsive element (TRE) and cAMP-responsive element (CRE), suggesting that in addition to regulation by RA receptors other transcription factors regulate RAR/β2 expression in EC cells. Furthermore, the availability of the mouse RARβ2 promoter should facilitate studies for transgene expression and gene targeting experiments in embryonic stem cells.</p

GATA6 expression in Barrett's oesophagus and oesophageal adenocarcinoma

BACKGROUND: Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gene amplification was recently linked with poor survival in oesophageal adenocarcinoma. AIM: To study the expression of GATA6 during Barrett's oesophagus development and malignant transformation. To determine the prognostic value of GATA6 in oesophageal adenocarcinoma. METHODS: Two retrospective cohorts were derived from the pathological archive of the University Medical Center Groningen. The first cohort contained 130 tissue samples of normal squamous epithelium, metaplasia, dysplasia and oesophageal adenocarcinoma. The second cohort consisted of a tissue microarray containing tissue from 92 oesophageal adenocarcinoma patients. Immunohistochemistry was used to examine GATA6 protein expression and to correlate GATA6 expression in oesophageal adenocarcinoma with overall and disease-free survival. RESULTS: The percentage of GATA6-positive cells was low in squamous epithelium (10%) but increased progressively in Barrett's oesophagus (30%, P<0.001) and high-grade dysplasia (82%, P=0.005). GATA6 expression was not associated with overall or disease-free survival in oesophageal adenocarcinoma patients (P=0.599 and P=0.700 respectively). CONCLUSION: GATA6 expression is progressively increased during Barrett's oesophagus development and its malignant transformation. However, no prognostic value of GATA6 expression could be found in oesophageal adenocarcinoma