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HCC and androgen receptor

Hui Ren, Bo Ren, Jiabin Zhang, Xiaofeng Zhang, Lixin Li, Lingzhan Meng, Zhijie Li, Jia Li, Yinjie Gao, Xuemei Ma
The expression of androgen receptor (AR) has been detected in hepatocellular cancer (HCC). However, there is no universal model detailing AR's function and mechanism in HCC. This study's results show that treatment with dihydrotestosterone (DHT), an endogenous androgen, promoted HCC cells' proliferation and up-regulated the transcription factor activity of ETS-1 (E26 transformation specific sequence 1), which mediates the migration and invasion of cancer cells via protein-protein interaction between AR and ETS-1...
December 12, 2017: Oncotarget
Hong Zhang, Xiaoxing Li, Yang Yang, Yanjie Zhang, Hui-Yun Wang, X F Steven Zheng
Hepatocellular carcinoma (HCC) is a male-dominant cancer and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous anti-androgen and -AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR-dependent transcriptome, stimulates oncogenic growth and determines therapeutic response to enzalutamide, a second generation of AR antagonist...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Liang Shi, Peijian Yan, Yuelong Liang, Yin Sun, Jiliang Shen, Senjun Zhou, Hui Lin, Xiao Liang, Xiujun Cai
Hepatocellular carcinoma (HCC) is a heterogeneous malignancy as a result of complex genetic and epigenetic alterations. HCC is characterized by a clear gender disparity for which there is lack of a clear mechanistic understanding. Androgen receptor (AR) is thought to be critical for such bias. Meanwhile, the potential function of circular RNA (circRNA), regulated by RNA editing enzyme, remained largely unknown in malignancy till now. By utilizing circRNA microarray survey coupled with in vitro analysis, we analyzed the influence of AR on circRNA expression in HCC...
November 16, 2017: Cell Death & Disease
Junjie Xu, Longbo Zheng, Jiang Chen, Yin Sun, Hui Lin, Ren-An Jin, Minyue Tang, Xiao Liang, Xiujun Cai
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR...
October 12, 2017: Cell Death & Disease
Tatsuo Kanda, Xia Jiang, Masato Nakamura, Yuki Haga, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Fumio Imazeki, Osamu Yokosuka
Hepatocellular carcinoma (HCC) is a predominantly male disease in which the androgen receptor (AR) serves an important pathogenic role in hepatocarcinogenesis. Fatty acid metabolism also contributes to hepatocarcinogenesis and is associated with the prognosis of cancer. The present study aimed to investigate the effects of the AR on fatty acid metabolism-associated gene expression in human hepatoma cell lines. AR-expression plasmids or control plasmids were transiently transfected into the human HCC cell lines Huh7 and HepG2...
June 2017: Oncology Letters
Tatsuo Kanda, Koji Takahashi, Masato Nakamura, Shingo Nakamoto, Shuang Wu, Yuki Haga, Reina Sasaki, Xia Jiang, Osamu Yokosuka
Hepatocellular carcinoma (HCC) is a male-dominant disease with poor prognosis. Sorafenib is the only approved systemic chemotherapeutic drug for patients with advanced HCC. Previous studies have shown that androgen and androgen receptor (AR) are involved in human hepatocarcinogenesis and the development of HCC. Here, we discuss the recent data on AR and HCC, and the combination of sorafenib and inhibitors of AR for advanced-HCC patients. Androgen-dependent and androgen-independent AR activation exist in human hepatocarcinogenesis...
May 5, 2017: Cancers
Mahmoud A Ali, Sahin Lacin, Reham Abdel-Wahab, Mark Uemura, Manal Hassan, Asif Rashid, Dan G Duda, Ahmed O Kaseb
The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC...
2017: OncoTargets and Therapy
Marco Cassano, Sandra Offner, Evarist Planet, Alessandra Piersigilli, Suk Min Jang, Hugues Henry, Markus B Geuking, Catherine Mooser, Kathy D McCoy, Andrew J Macpherson, Didier Trono
Hepatocellular carcinoma (HCC) represents the fifth-most common form of cancer worldwide and carries a high mortality rate attributed to lack of effective treatment. Males are 8 times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28(hep-/-) mice display sex-specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males...
July 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xiao-Fei Zhang, Xin Yang, Hu-Liang Jia, Wen-Wei Zhu, Lu Lu, Wei Shi, Hao Zhang, Jin-Hong Chen, Yi-Feng Tao, Zheng-Xin Wang, Jun Yang, Lian-Xin Wang, Ming Lu, Yan Zheng, Jing Zhao, Qiong-Zhu Dong, Lun-Xiu Qin
OBJECTIVE: The expression of B-cell lymphoma 2 (Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma (HCC) patients was examined to verify the high incidence of HCC in males...
December 2016: Cancer Biology & Medicine
Junjie Xu, Hui Lin, Gonghui Li, Yin Sun, Jiang Chen, Liang Shi, Xiujun Cai, Chawnshang Chang
The androgen receptor (AR) was found to suppress hepatocellular carcinoma (HCC) metastasis at late stages. Due to this discovery, we searched for some AR enhancers to increase the efficacy of Sorafenib chemotherapy, and identified the microRNA (miR)-367-3p, whose expression is positively correlated with AR expression in advanced HCC, as an HCC metastasis suppressor. Combining miR-367-3p with Sorafenib showed better efficacy to suppress HCC cell invasion in vitro and in vivo. Mechanism dissection revealed that miR-367-3p could increase AR expression via directly targeting the 3'UTR of MDM2 to decrease MDM2 protein expression...
October 2016: EBioMedicine
Tatsuo Kanda, Osamu Yokosuka
Hepatocellular carcinoma (HCC) is one of the male-dominant liver diseases with poor prognosis, although treatments for HCC have been progressing in the past decades. Androgen receptor (AR) is a member of the nuclear receptor superfamily. Previous studies reported that AR was expressed in human HCC and non-HCC tissues. AR is activated both ligand-dependently and ligand-independently. The latter is associated with a mitogen-activated protein kinase-, v-akt murine thymoma viral oncogene homolog 1-, or signal-transducer and activator of transcription-signaling pathway, which has been implicated in the development of HCC...
2015: Journal of Hepatocellular Carcinoma
Hsueh-Chou Lai, Chun-Chieh Yeh, Long-Bin Jeng, Shang-Fen Huang, Pei-Ying Liao, Fu-Ju Lei, Wei-Chun Cheng, Cheng-Lung Hsu, Xiujun Cai, Chawnshang Chang, Wen-Lung Ma
PURPOSE: Although hepatectomy and liver transplantation surgery for hepatocellular carcinoma (HCC) are effective treatment modalities, the risk of recurrence remains high, particularly in patients with a high number of circulating tumor cells (CTCs) expressing cancer stem/progenitor cell markers. Androgen receptor (AR) signaling has been shown to suppress HCC metastasis in rodent models of HCC. In this study, we investigated whether AR is associated with postoperative HCC recurrence. EXPERIMENTAL DESIGN: CTCs were obtained from patients with HCC who had undergone hepatectomy to investigate whether they are associated with disease outcome...
July 19, 2016: Oncotarget
Lupin Jiang, Juanjuan Shan, Junjie Shen, Yanzhou Wang, Ping Yan, Limei Liu, Wenxu Zhao, Yanmin Xu, Wei Zhu, Li Su, Jun Chen, Feifei Cheng, Hong Yao, Huicheng Xu, Cheng Qian, Zhiqing Liang
Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers. The HCC incidence gets a strong sexual dimorphism as men are the major sufferers in this disaster. Although several studies have uncovered the presentative correlation between the axis of androgen/androgen receptor (AR) and HCC incidence, the mechanism is still largely unknown. Cancer stem cells (CSCs) are a small subgroup of cancer cells contributing to multiple tumors malignant behaviors, which play an important role in oncogenesis of various cancers including HCC...
June 14, 2016: Oncotarget
Liang Shi, Hui Lin, Gonghui Li, Ren-An Jin, Junjie Xu, Yin Sun, Wen-Lung Ma, Shuyuan Yeh, Xiujun Cai, Chawnshang Chang
Gender disparity has long been considered as a key to fully understand hepatocellular carcinoma (HCC) development. At the same time, immunotherapy related to IL12 still need more investigation before being applied in clinical settings. The aim of this study is to investigate the influence of the androgen receptor (AR) on natural killer (NK) cell-related innate immune surveillance in liver cancer, and provide a novel therapeutic approach to suppress HCC via altering IL12A. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mouse model, we identified the role of AR in modulating NK cell cytotoxicity...
April 2016: Molecular Cancer Therapeutics
Liang Shi, Hui Lin, Gonghui Li, Yin Sun, Jiliang Shen, Junjie Xu, Changyi Lin, Shuyuan Yeh, Xiujun Cai, Chawnshang Chang
The aim of this study is to investigate the influence of cisplatin on the efficacy of natural killer (NK) cells immunotherapy to suppress HCC progression, and provide valuable information on better application of cisplatin in clinical settings. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mice model, we identified the role of cisplatin in modulating NK cells cytotoxicity. Luciferase report assay and chromatin immunoprecipitation assay were applied for mechanism dissection...
April 1, 2016: Cancer Letters
Sheng-Han Wang, Shiou-Hwei Yeh, Chung-Wai Shiau, Kuen-Feng Chen, Wei-Hsiang Lin, Ting-Fen Tsai, Yuan-Chi Teng, Ding-Shinn Chen, Pei-Jer Chen
BACKGROUND: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) shows a higher incidence in men, mainly because of hepatitis B X (HBx)-mediated enhancement of androgen receptor (AR) activity. We aimed to examine this pathway in hepatocarcinogenesis and to identify drug(s) specifically blocking this carcinogenic event in the liver. METHODS: HBx transgenic mice that spontaneously develop HCC (n = 28-34 per group) were used, either by knockout of hepatic AR or by castration...
October 2015: Journal of the National Cancer Institute
Hanaa H Ahmed, Wafaa Gh Shousha, Aziza B Shalby, Hatem A El-Mezayen, Nora N Ismaiel, Nadia S Mahmoud
The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Y E Tian, X U Xie, Yao Lin, Guang Tan, W U Zhong
Previous studies have indicated that males are at a higher risk of developing hepatocellular carcinoma (HCC) compared with females. Identifying the factors that cause this gender-specific difference in the incidence of HCC has long been considered important for revealing the molecular mechanisms involved in hepatocarcinogenesis. Given the unprecedented tools that are now available for molecular research, genetic studies have established that the androgen receptor (AR) may be partly responsible for gender disparity in HCC...
May 2015: Oncology Letters
Zhangwei Tong, Ming Li, Wei Wang, Pingli Mo, Li Yu, Kun Liu, Wenjing Ren, Wengang Li, Hao Zhang, Jianming Xu, Chundong Yu
Steroid receptor coactivator 1 (SRC-1) is a transcriptional coactivator not only for steroid receptors, such as androgen receptor and estrogen receptor, but also for other transcription factors. SRC-1 has been shown to play an important role in the progression of breast cancer and prostate cancer. However, its role in liver cancer progression remains unknown. In this study, we report that SRC-1 was overexpressed in 25 (62.5%) of 40 human hepatocellular carcinoma (HCC) specimens. Down-regulation of SRC-1 decreased HCC cell proliferation and impaired tumor maintenance in HCC xenografts...
July 24, 2015: Journal of Biological Chemistry
Yan Zhang, Yucheng Shen, Bin Cao, Aiting Yan, Haoming Ji
The aim of the present study was to investigate the potential roles of the androgen receptor (AR) and matrix metalloproteinase (MMP)-2 and MMP-9 in hepatocellular carcinoma (HCC) tissues and whether their expression could be used as a predictor of the invasion and stage of cancer. The expression levels of AR, MMP-2 and MMP-9 in HCC tissues and tissues adjacent to the tumor were measured by immunohistochemical staining assay. The expression rates of AR, MMP-2 and MMP-9 in the HCC tissue were 76.67, 73.33 and 76...
March 2015: Experimental and Therapeutic Medicine
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