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A Picon

Publications and source records attributed to A Picon.

4 recordsLinked to original sources
PubMed1997

High expression of the POU factor Brn3a in aggressive neuroendocrine tumors.

A new family of POU transcription factors called Brn plays a role in development of the brain and some neuroendocrine structure. Because a member of this family, Brn3a, is present in the ACTH-producing mouse pituitary tumor AtT-20, binds to POMC promoter, and stimulates its activity, we studied its human homolog in ACTH-secreting or nonsecreting tumors of pituitary and bronchial origins. A specific and quantitative reverse transcription-PCR assay was developed to assess Brn3a transcripts in tumor ribonucleic acid. Brn3a transcript levels were invariably low (< 5 x 10(-6) arbitrary units) in four GH-, two PRL-, three gonadotropin-, and seven of eight ACTH-producing pituitary adenomas. A single highly invasive ACTH-secreting pituitary adenoma in a patient who ultimately died with liver metastases, and the mouse corticotroph tumor cell line AtT-20 had high Brn3a transcripts levels at 3 x 10(-5) and 4 x 10(-4) arbitrary units, respectively. Five typical bronchial carcinoids had barely detectable levels (< 5 x 10(-6) arbitrary units), whereas seven of eight small cell carcinomas of the lung (SCCLs) had extremely high levels (between 10(-3)-10(-1) arbitrary units); six of seven atypical bronchial carcinoids had intermediate values, between 10(-6) and 5 x 10(-3) arbitrary units. Although nine bronchial tumors produced POMC, there was no association between Brn3a levels and POMC gene expression; the two tumors with the highest POMC messenger ribonucleic acid contents were two bronchial carcinoids with barely detectable Brn3a levels. A gel mobility shift assay was performed with a rat CRH promoter probe that binds Brn3a; extracts of the POMC-producing human SCCL line DMS-79, which contained high levels of Brn3a transcripts, generated the same specific complex as did AtT-20 cell extracts. These data show that Brn3a gene expression in neuroendocrine tumors is not correlated with POMC gene expression; rather, it is strikingly elevated in the highly aggressive tumors, independently of their POMC status and their pituitary or nonpituitary origin.

Adenoma↗
PubMed1995

Functional analysis of the human pro-opiomelanocortin promoter in the small cell lung carcinoma cell line DMS-79.

DMS-79 is a human cell line derived from a small cell lung carcinoma (SCLC), which expresses the pro-opiomelanocortin (POMC) gene. We took it as a model in which to study the mechanism of POMC gene expression in these tumors: precursor processing is altered and gene expression is essentially unresponsive to glucocorticoids. POMC gene structure appeared normal by Southern blot analysis, indicating that gene rearrangement was not responsible for its expression in DMS-79. Indeed, using transient expression of human POMC-luciferase fusion genes in DMS-79, we showed that (1) the normal human POMC promoter was functional in DMS-79, and (2) the same proximal promoter region (-417; + 21) produced the full transcriptional activity in DMS-79 and in the mouse pituitary cell line AtT-20. Progressive 5' deletion analysis revealed differences between AtT-20 and DMS-79: region (-611; -376) was active in AtT-20 and not in DMS-79, whereas region (-95; -161) was active in both cell lines and (-376; -417) was only active in DMS-79. The latter partially overlaps a motif homologous to the DE-2 rat element which confers the tissue-specific expression of POMC in AtT-20 cells; however, this motif had no effect in DMS-79. These data suggest that POMC gene transcription is achieved through a different set of transacting factors in DMS-79 and AtT-20. Altogether, our results provide evidence that DMS-79 is a valid model of tumors responsible for the ectopic ACTH syndrome and that the mechanism of POMC gene expression in these SCLC cells is different from that in pituitary cells.

Animals↗
PubMed1990

Renal response to a protein meal in children with single kidneys.

The renal response of healthy adults to an oral protein load results in a significant increase of renal plasma flow (RPF) and glomerular filtration rate (GFR) 100 to 150 min after the meal. The renal response to protein loading of single kidney adults is unclear and it has not been evaluated yet in children. Therefore, we studied 8 children 10.2 +/- 1.1 years old, 6.7 +/- 1.41 years after nephrectomy (SK) and 4 healthy children (C). RPF was estimated by para-amino-hippurate clearance (Cpah) and GFR by inulin clearance (Cin) before and after an oral protein load of 1.5 g protein/kg body wt and expressed in ml/min/1.73 m2 BSA. Mean baseline Cin were similar in SK and in C (90 +/- 8 vs 103 +/- 12) while baseline Cpah was lower in SK (339 +/- 19 vs 481 +/- 36, p less than 0.005). After the meal GFR and RPF increased significantly in C (155 +/- 18 and 783 +/- 68, p less than 0.005 and p less than 0.05 vs baseline values, respectively) whereas no significant GFR and RPF changes were seen in SK (81 +/- 9 and 350 +/- 42, respectively). However, the 3 SK children with lower protein intake showed a mild vasodilating response. We conclude that in single kidney children hyperfiltration occurs at baseline conditions and the renal response to acute protein loading is partially or completely blunted, being modulated by protein intake.

Adolescent↗