Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein

Background: Although the founding members of the INhibitor of Growth (ING) family of histone mark readers, ING1 and ING2, were defined as tumour suppressors in animal models, the role of other ING proteins in cellular proliferation and cancer progression is unclear. Methods: We transduced ex vivo benign prostate hyperplasia tissues with inducible lentiviral particles to express ING proteins. Proliferation was assessed by H3S10phos immunohistochemistry (IHC). The expression of ING3 was assessed by IHC on a human prostate cancer tissue microarray (TMA). Gene expression was measured by DNA microarray and validated by real-time qPCR. Results: We found that ING3 stimulates cellular proliferation in ex vivo tissues, suggesting that ING3 could be oncogenic. Indeed, ING3 overexpression transformed normal human dermal fibroblasts. We observed elevated levels of ING3 in prostate cancer samples, which correlated with poorer patient survival. Consistent with an oncogenic role, gene-silencing experiments revealed that ING3 is required for the proliferation of breast, ovarian, and prostate cancer cells. Finally, ING3 controls the expression of an intricate network of cell cycle genes by associating with chromatin modifiers and the H3K4me3 mark at transcriptional start sites. Conclusions: Our investigations create a shift in the prevailing view that ING proteins are tumour suppressors and redefine ING3 as an oncoprotein

Histological changes in the pancreas following administration of ethanolic extract of Alchornea cordifolia leaf in alloxan-induced diabetic Wistar rats

Twenty-four wistar rats weighing between 150 and 170g were used in this research work. They were divided into four groups A, B, C, and D of six rats each. Diabetes was induced in Groups B, C, and D using a single intraperitoneal injection of 150mg/kg of Alloxan after an overnight fast. Group A served as the normal control while Group B served as the diabetic control and each received 0.5ml of normal saline daily. Groups C and D received 250mg/kgbwt/day and 500mg/kg /day of the plant extract respectively through orogastric intubation. All the animals were given normal rat chow and water freely. The experiment lasted for 28 days. The animals were anaesthetized using chloroform inhalation and the peritoneum stripped open and the pancreas removed and prepared for histological observation using haematoxylin and eosin staining technique. Histology showed regenerative changes of pancreatic islet cell at a dose of 500 mg/kg/day