Gene Expression 16(3) Abstracts

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Gene Expression, Vol. 16, pp. 101–108, 2015
1052-2166/13 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/105221615X14181438356292
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Role of Hepatocyte Nuclear Factor 4α (HNF4α) in Cell Proliferation and Cancer

Chad Walesky*† and Udayan Apte*

*Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
†Department of Medicine – Genetics Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Hepatocyte nuclear factor 4α (HNF4α) is an orphan nuclear receptor commonly known as the master regulator of hepatic differentiation, owing to the large number of hepatocyte-specific genes it regulates. Whereas the role of HNF4α in hepatocyte differentiation is well recognized and extensively studied, its role in regulation of cell proliferation is relatively less known. Recent studies have revealed that HNF4α inhibits proliferation not only of hepatocytes but also cells in colon and kidney. Further, a growing number of studies have demonstrated that inhibition or loss of HNF4α promotes tumorigenesis in the liver and colon, and reexpression of HNF4α results in decreased cancer growth. Studies using tissue-specific conditional knockout mice, knock-in studies, and combinatorial bioinformatics of RNA/ChIP-sequencing data indicate that the mechanisms of HNF4α-mediated inhibition of cell proliferation are multifold, involving epigenetic repression of promitogenic genes, significant cross talk with other cell cycle regulators including c-Myc and cyclin D1, and regulation of miRNAs. Furthermore, studies indicate that posttranslational modifications of HNF4α may change its activity and may be at the core of its dual role as a differentiation factor and repressor of proliferation. This review summarizes recent findings on the role of HNF4α in cell proliferation and highlights the newly understood function of this old receptor.

Key words: c-Myc; Proliferating cell nuclear antigen (PCNA); Diethylnitrosamine; Hepatocytes; Hepatocellular carcinoma (HCC)

Address correspondence to Udayan Apte, Ph.D., D.A.B.T., Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, MS1018, Kansas City, KS 66160, USA. Tel: +1 (913) 588-9247; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 109–127, 2015
1052-2166/13 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/105221615X14181438356210
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

PDGFRα in Liver Pathophysiology: Emerging Roles in Development, Regeneration, Fibrosis, and Cancer

Alexander Kikuchi and Satdarshan Pal Monga

Department of Pathology and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Platelet-derived growth factor receptor α (PDGFRα) is an isoform of the PDGFR family of tyrosine kinase receptors involved in cell proliferation, survival, differentiation, and growth. In this review, we highlight the role of PDGFRα and the current evidence of its expression and activities in liver development, regeneration, and pathology—including fibrosis, cirrhosis, and liver cancer. Studies elucidating PDGFRα signaling in processes ranging from profibrotic signaling, angiogenesis, and oxidative stress to epithelial-to-mesenchymal transition point toward PDGFRα as a potential therapeutic target in various hepatic pathologies, including hepatic fibrosis and liver cancer. Furthermore, PDGFRα localization and modulation during liver development and regeneration may lend insight into its potential roles in various pathologic states. We will also briefly discuss some of the current targeted treatments for PDGFRα, including multireceptor tyrosine kinase inhibitors and PDGFRα-specific inhibitors.

Key words: Platelet-derived growth factor (PDGF); Liver development; Liver regeneration; Hepatic fibrosis; Cirrhosis; Hepatocellular carcinoma; Cholangiocarcinoma; β-Catenin; NF-κB; Transforming growth factor-β (TGF-β); Oxidative stress; Sorafenib; IMC-3G3; APA5

Address correspondence to Satdarshan Pal Singh Monga, M.D., Vice Chair of Experimental Pathology, Endowed Chair of Experimental Pathology, Professor of Pathology and Medicine (Gastroenterology, Hepatology, and Nutrition), University of Pittsburgh School of Medicine, 200 Lothrop Street S-422 BST, Pittsburgh, PA 15261, USA. Tel: +1 (412) 648-9966; Fax: +1 (412) 648-1916; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 129–135, 2015
1052-2166/13 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/105221615X14181438356256
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

The Long Journey of TCL1 Transgenic Mice: Lessons Learned in the Last 15 Years

Yuri Pekarsky, Alessandra DruscoPrasanthi Kumchala, Carlo M. Croce, and Nicola Zanesi

MVIMG, The Ohio State University, Columbus, OH, USA

The first transgenic mouse of the TCL1 oncogene was described more than 15 years ago, and since then, the overexpression of the gene in T- and B-cells in vivo has been extensively studied to reveal the molecular details in the pathogenesis of some lymphocytic leukemias. This review discusses the main features of the original TCL1 models and the different lines of research successively developed with particular attention to genetically compound mice and the therapeutic applications in drug development.

Key words: Lck-TCL1; B-Cell; Em-TCL1; Chronic lymphocytic leukemia (CLL); Mouse models

Address correspondence to Nicola Zanesi, Ph.D., 1094 Biomedical Research Tower, 460 W 12th Ave., Columbus, OH 43210, USA. Tel: +1-614-292-3318; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 137–144, 2015
1052-2166/13 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/105221615X14181440065490
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Single Nucleotide Polymorphisms in HIF-1α Gene and Residual Ridge Resorption (RRR) of Mandible in Korean Population

J. Paek,* Y. Oh,† J. Kim,† and J.-H. Lee†

*Department of Prosthodontics, Kyung Hee University Dental Hospital, Seoul, Korea
†Department of Prosthodontics, College of Dentistry, Yonsei University, Seoul, Korea

Tooth extraction is a routine surgical procedure in dental treatment. As a wound healing process after tooth extraction, a saddle-shaped residual ridge forms due to bone formation in the extraction socket and localized bone resorption on the external surface of the jawbone. The residual ridge is subjected to continuous bone resorption with substantial differences among individuals. In some cases, it results in excessive bone atrophy, which complicates dental restorative treatment. This unique oral wound healing process may be influenced by factors that are specific to oral tissue. HIF expression is different in oral wound healing compared to that of skin wounds. The objective of this study was to examine a genetic association between SNP of the HIF-1α gene, which is known to have high genetic diversity, and the residual ridge resorption (RRR). Two hundred and two Korean subjects (70.80 ± 9.40 years) with partially or completely edentulous mandible were recruited, and edentulous mandibular bone height was measured following the protocol of the American College of Prosthodontists. The HIF-1α allele was directly sequenced in 24 subjects resulting in the variants over 5% frequency in 95% likelihood, whereas tag-SNPs were selected to perform analysis for the remaining population. Student’s t-test and ANOVA were used for statistical analysis to examine the association between the SNPs and the RRR. Four novel variants were discovered, and a minor allele of rs11549467 was associated with the RRR of the subjects (p = 0.028). rs11549467 increases HIF-1α transactivity, enhancing angiogenesis and increasing new vessel formation. Thus, rs11549467 may play an important role in the disturbed bone remodeling balance resulting in RRR. Results of this study may be useful in developing novel genetic diagnostic tests and identifying Koreans susceptible to developing excessive jawbone atrophy after dental extraction. Most importantly, early screening using genetic information will rescue susceptible patients from the vulnerable situation of excessive jawbone atrophy where no effective prosthetic treatment is available.

Key words: Single nucleotide polymorphism (SNP); HIF-1α; Residual ridge resorption (RRR); Edentulous mandible; Atrophy

Address correspondence to Jae-Hoon Lee, D.D.S., M.S., Ph.D., Department of Prosthodontics, College of Dentistry, Yonsei University, 50 Yonsei-roSeodaemoon-gu, Seoul 120-752, Korea. Tel: +82-2-2228-3159; Fax: +82-2-312-3598; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 145–153, 2015
1052-2166/13 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/105221615X14181438356337
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Comprehensive Analysis of the GABAergic System Gene Expression Profile in the Anterior Cingulate Cortex of Mice With Paclitaxel-Induced Neuropathic Pain

Willias Masocha

Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

The supraspinal pathophysiology of the painful neuropathy induced by paclitaxel, a chemotherapeutic agent, is not well understood. The γ-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of neuropathic pain. Gene expression of GABAergic system molecules was examined in the anterior cingulate cortex (ACC) of mice brains, by real-time PCR, during paclitaxel-induced neuropathic pain, because this area is involved in pain perception and modulation that might contribute to neuropathic pain. Paclitaxel treatment resulted in thermal hyperalgesia and in increased GABA transporter-1 (GAT-1) mRNA expression, but not that of other GABA transporters or GABAergic enzymes in the ACC compared to vehicle treatment. Among the 18 GABAA
receptor subunits analyzed, only β2, β3, δ, and γ2 had increased mRNA levels, and for the GABAB receptor subunit, only GABAB2 had increased mRNA levels in the ACC of paclitaxel-treated mice, whereas the rest of the GABA receptor subunits were not altered. The mRNA expression of GABAA receptor subunits α6, θ, π, ρ1, ρ2, and ρ3 were not detected in the ACC. In conclusion, these data show that during paclitaxel-induced neuropathic pain there is significant increase in GAT-1 expression in the ACC. GAT-1 is the main transporter of GABA from the synapse, and thus its increased expression possibly results in less GABA at the synapse and dysregulation of the GABAergic system. GAT-1 is a potential therapeutic target for managing paclitaxel-induced neuropathic pain.

Key words: Chemotherapy-induced neuropathic pain; Paclitaxel; Anterior cingulate cortex (ACC); γ-Aminobutyric acid (GABA); GABA transporter; GABA receptor

Address correspondence to Willias Masocha, Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923 Safat, 13110 Kuwait. Tel: +965 2498 6078; Fax: +965 2 534 2807; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it