Molecular Phenotyping of Kidney Biopsies By Global Gene Expression Tightly Correlates With Histology Phenotypes and Long-Term Outcomes.

Long-term exposure to piperonyl butoxide (PBO) induces multiple nodular masses along with hepatocellular tumors in the liver of mice. The histopathological features of the nodules led to our diagnosis of nodular regenerative hepatocellular hyperplasia (NRH). However, because of the lack of data on the biological characteristics of NRH, whether this lesion is truly nonneoplastic remains unknown. In this study, the molecular characteristics of NRH were compared with those of hepatocellular adenoma (HCA) by global gene expression analysis. Six-week-old male ICR mice were fed a diet containing 6,000 ppm PBO for 43 weeks to induce NRH and HCA development. Complementary DNA microarray analysis was performed using messenger RNA extracted from NRH and HCA frozen sections collected by laser microdissection. Hierarchical cluster analysis showed that all NRH samples clustered together but were separate from the HCA cluster. Pathway analysis revealed activation of the cell cycle and Delta–Notch signaling in both lesions, but the latter was more upregulated in HCA. Downregulation of cytochrome p450 enzymes was observed in NRH, but not in HCA. These results imply that NRH differs from HCA in terms of not only morphological but also molecular characteristics.

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Long-term global gene expression patterns in irradiated human lymphocytes

Carcinogenesis ◽

10.1093/carcin/bgg134 ◽

2003 ◽

Vol 24 (11) ◽

pp. 1837-1845 ◽

Cited By ~ 39

Author(s):

S. Falt

Keyword(s):

Gene Expression ◽

Human Lymphocytes ◽

Expression Patterns ◽

Global Gene Expression ◽

Gene Expression Patterns

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Effects of Short and Long-Term Soy Protein Isolate Intake on Hepatic Cytochrome P450 Expression in Obese Zucker Rats

Current Developments in Nutrition ◽

10.1093/cdn/nzab055_035 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1225-1225

Author(s):

Melisa Kozaczek ◽

Walter Bottje ◽

Reza Hakkak

Keyword(s):

Gene Expression ◽

Soy Protein ◽

Soy Protein Isolate ◽

Global Gene Expression ◽

Protein Isolate ◽

Zucker Rats ◽

Z Score ◽

Short And Long Term ◽

Obese Zucker Rats

Abstract Objectives To determine the effects feeding for 8 (short-term) and 16 weeks (long-term) soy protein isolate on hepatic CYP gene expression. Methods 7-weeks old rats were randomly assigned to either a casein (CAS) or a soy protein isolate (SPI) diet. They were provided the diets ad libitum for 8 and 16 weeks. Rats were euthanized and livers were stored at − 80°C. RNA was extracted from liver samples, and sequenced to obtain transcriptomic data (RNAseq). Ingenuity Pathway Analysis software (IPA, Qiagen, CA) was used in the analysis of global gene expression data. This analysis includes predictions of activation or inhibition of molecules or upstream regulators and functions based on a generated z-score and p-value of overlap (P = 0.05). Z-scores were consider significant when > 2 (activation) and < −2 (inhibition). Results Comparing short- vs long-term feeding revealed an increase in the number of down-regulated CYP genes from only 3 at 8 weeks of SPI diet to 10 at 16 weeks of same diet (P < 0.05). In contrast, upregulated CYP gene numbers showed a small increase in long-term SPI diet compared to short-term, from 14 genes at 8 weeks to 17 genes at 16 weeks (P < 0.05). In addition, we present a predicted activation of the transcription factor Aryl hydrocarbon receptor (AHR, activation z-score = 2.146, P = 4.20E-11), linked to the subsequent activation or up-regulation of various CYPs genes, indirectly leading to the activation and inhibition of two main metabolic functions under SPI feeding: conversion of lipid (lipid metabolism) –predicted to be activated (z-score = 2.089, P = 2.77E-08), and recruitment of phagocytes (inflammatory response) –predicted to be inhibited (z-score = −2.311, P = 2.10E-05). Conclusions Through global gene expression analysis we showed that gene expression of drug-metabolizing cytochrome P450 genes was modified in genetically obese Zucker rats after being fed a soy-based diet for short- and long-term, and that this change could have an important role in attenuation of liver steatosis. Further research is needed to corroborate these results. Funding Sources This study was supported in part by the College of Medicine's University Medical Group (RH) and the Arkansas Biosciences Institute (WB, RH).

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Intrinsic Subtypes from the PAM50 Gene Expression Assay in a Population-Based Breast Cancer Survivor Cohort: Prognostication of Short- and Long-term Outcomes

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-13-1017 ◽

2014 ◽

Vol 23 (5) ◽

pp. 725-734 ◽

Cited By ~ 29

Author(s):

Bette J. Caan ◽

Carol Sweeney ◽

Laurel A. Habel ◽

Marilyn L. Kwan ◽

Candyce H. Kroenke ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Survivor ◽

Breast Cancer Survivor ◽

Population Based ◽

Long Term Outcomes ◽

Intrinsic Subtypes ◽

Gene Expression Assay ◽

Short And Long Term

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Phenotypic and global gene expression profile changes between low passage and high passage MIN-6 cells

Journal of Endocrinology ◽

10.1677/joe.1.06894 ◽

2006 ◽

Vol 191 (3) ◽

pp. 665-676 ◽

Cited By ~ 36

Author(s):

Lorraine O’Driscoll ◽

Patrick Gammell ◽

Eadaoin McKiernan ◽

Eoin Ryan ◽

Per Bendix Jeppesen ◽

...

Keyword(s):

Gene Expression ◽

Alkaline Phosphatase ◽

Global Gene Expression ◽

Stem Cell Marker ◽

Β Cell ◽

High Passage ◽

Long Term Culture ◽

Low Passage

The long-term potential to routinely use replacement β cells/islets as cell therapy for type 1 diabetes relies on our ability to culture such cells/islets, in vitro, while maintaining their functional status. Previous β cell studies, by ourselves and other researchers, have indicated that the glucose-stimulated insulin secretion (GSIS) phenotype is relatively unstable, in long-term culture. This study aimed to investigate phenotypic and gene expression changes associated with this loss of GSIS, using the MIN-6 cell line as model. Phenotypic differences between MIN-6(L, low passage) and MIN-6(H, high passage) were determined by ELISA (assessing GSIS and cellular (pro)insulin content), proliferation assays, phase contrast light microscopy and analysis of alkaline phosphatase expression. Differential mRNA expression was investigated using microarray, bioinformatics and real-time PCR technologies. Long-term culture was found to be associated with many phenotypic changes, including changes in growth rate and cellular morphology, as well as loss of GSIS. Microarray analyses indicate expression of many mRNAs, including many involved in regulated secretion, adhesion and proliferation, to be significantly affected by passaging/ long-term culture. Loss/reduced levels, in high passage cells, of certain transcripts associated with the mature β cell, together with increased levels of neuron/glia-associated mRNAs, suggest that, with time in culture, MIN-6 cells may revert to an early (possibly multi-potential), poorly differentiated, ‘precursor-like’ cell type. This observation is supported by increased expression of the stem cell marker, alkaline phosphatase.

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