Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN.

The mouse haematopoietic stem cell (SC) regulator Latexin (LXN) is the only known homologue of the retinoic acid receptor responder 1 (RARRES1) gene. Both genes lie adjacent on chromosome 3 and differ mostly by the presence of a transmembrane domain in RARRES1. Despite their homology, it is not known whether they possess similar regulatory mechanisms, cellular localization and function. Here, we identified RARRES1 and LXN as highly significantly downregulated genes in human prostate SCs, whose expression was induced by the pro-differentiation agent all-trans retinoic acid (atRA). AtRA induced expression in the most differentiated cells compared with the SC fraction, suggesting that this subpopulation was less responsive to atRA. Small interfering RNA suppression of RARRES1 and LXN enhanced the SC properties of primary prostate cultures, as shown by a significant increase in their colony-forming ability. Expression of both RARRES1 and LXN was co-ordinately repressed by DNA methylation in prostate cancer cell lines and inhibition of RARRES1 and LXN increased the invasive capacity of primary prostate cultures, which also fully rescued an inhibitory effect induced by atRA. Moreover, we showed that RARRES1 and LXN reside within different sub-cellular compartments, providing evidence that RARRES1 is not a plasma membrane protein as previously supposed but is located primarily in the endoplasmic reticulum; whereas LXN was detected in the nucleus of prostate epithelial cells. Thus, LXN and RARRES1 are potential tumour suppressor genes, which are co-ordinately regulated, SC-silenced genes functioning to suppress invasion and colony-forming ability of prostate cancer cells; yet the proteins reside within different sub-cellular compartments.

Comparison of three methods of thiamine supplementation by measurement of urinary thiamine excretion in sheep.

The relative efficacy of thiamine supplementation to sheep by injection, subcutaneous implant and orally administered protected thiamine bolus was compared in two experiments using a grass and hay ration and a ration containing bracken rhizomes to induce thiamine deficiency. In both experiments, urinary excretion of thiamine was significantly higher in supplemented sheep than in the controls, and in sheep supplemented by injection than in sheep supplemented by implant or protected boluses. Thiamine excretion was lower in sheep fed the ration containing bracken rhizomes than in sheep fed the grass ration.

The vitamin B6 status of pigs given a diet containing linseed meal.

1. Pigs consuming a diet containing 300 g linseed meal/kg and a pyridoxine supplement showed greater growth, nitrogen retention, blood packed cell volume and haemoglobin than those receiving only the basal diet. 2. Tryptophan-load tests on unsupplemented pigs revealed an increased excretion of kynurenine, Nalpha-acetylkynurenine and xanthurenic acid compared to those receiving additional pyridoxine. 3. The results suggest that the unsupplemented pigs were marginally deficient in vitamin B6. 4. When the same diet was fed to rats there was no evidence of vitamin B6 deficiency.