Advanced Search
WANG Ruihua, CAI Shiliang, LIU Donghong, CHEN Hongsen, CAO Guangwen. Research Progress of Androgen/Androgen Receptor Signaling Pathway in Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2023, 50(2): 180-185. DOI: 10.3971/j.issn.1000-8578.2023.22.0714
Citation: WANG Ruihua, CAI Shiliang, LIU Donghong, CHEN Hongsen, CAO Guangwen. Research Progress of Androgen/Androgen Receptor Signaling Pathway in Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2023, 50(2): 180-185. DOI: 10.3971/j.issn.1000-8578.2023.22.0714
shu

Research Progress of Androgen/Androgen Receptor Signaling Pathway in Hepatocellular Carcinoma

  • 1.

    Department of Epidemiology, Jinan University, Guangzhou 510632, China

  • 2.

    Department of Epidemiology, Naval Medical University, Shanghai 200433, China

  • 3.

    Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, China

Funding: 

National Key Basic Research Program of China (973 Program) 2015CB554000

Shanghai Key Discipline of Public Health GWV-10.1-XK17

The National Natural Science Founding of China 91529305

The National Natural Science Founding of China 81520108021

The National Natural Science Founding of China 81673250

The National Natural Science Founding of China 82003538

More Information
  • Corresponding author:

    CAO Guangwen, E-mail: gcao@smmu.edu.cn

  • Received Date: June 26, 2022
  • Revised Date: September 04, 2022
  • Available Online: January 12, 2024
    Graphical Abstract
    • Abstract

  • Hepatocellular carcinoma (HCC) is a kind of primary liver cancer with a high mortality rate. In China, the incidence ratio in males to females with HCC is 2:1–5:1. The difference in sex hormone pathways between males and females and the interaction between androgen/androgen receptors and HBV can lead to an incidence difference between males and females with HCC. Hence, the androgen/androgen receptor oncogenic pathway in hepatocellular carcinoma has received considerable attention. This review mainly summarizes the recent research progress on the androgen/androgen receptor oncogenic pathway in hepatocellular carcinoma.

    • FullText(HTML)

  • Competing interests: The authors declare that they have no competing interests.

    • References (61)
  • [1]
    Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
    [2]
    曹毛毛, 李贺, 孙殿钦, 等. 全球肝癌2020年流行病学现状[J]. 中华肿瘤防治杂志, 2022, 29(5): 322-328. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL202205003.htm

    Cao MM, Li H, Sun DQ, et al. Global epidemiology of liver cancer in 2020[J]. Zhonghua Zhong Liu Fang Zhi Za Zhi, 2022, 29(5): 322-328. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL202205003.htm
    [3]
    刘宗超, 李哲轩, 张阳, 等. 2020全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2021, 7(2): 1-13. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLZD202102001.htm

    Liu ZC, Li ZX, Zhang Y, et al. Interpretation on the report of Global Cancer Statistics 2020[J]. Zhong Liu Zong He Zhi Liao Dian Zi Za Zhi, 2021, 7(2): 1-13. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLZD202102001.htm
    [4]
    Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: an overview[J]. Int J Cancer, 2021, 5. Online ahead of print.
    [5]
    Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. doi: 10.3322/caac.21338
    [6]
    查旭东, 刘文斌, 曹广文. 肝细胞癌发生及预后性别差异的相关危险因素[J]. 上海预防医学, 2017, 29(4): 253-256. https://www.cnki.com.cn/Article/CJFDTOTAL-SHYI201704002.htm

    Zha XD, Liu WB, Cao GW, et al. Risk factors related to the sexual dimorphism in the incidence and prognosis of hepatocellular carcinoma[J]. Shanghai Yu Fang Yi Xue, 2017, 29(4): 253-256. https://www.cnki.com.cn/Article/CJFDTOTAL-SHYI201704002.htm
    [7]
    Salvi S, Bonafè M, Bravaccini S. Androgen receptor in breast cancer: a wolf in sheep's clothing? A lesson from prostate cancer[J]. Semin Cancer Biol, 2020, 60: 132-137. doi: 10.1016/j.semcancer.2019.04.002
    [8]
    Aurilio G, Cimadamore A, Mazzucchelli R, et al. Androgen receptor signaling pathway in prostate cancer: from genetics to clinical applications[J]. Cells, 2020, 9(12): 2653. doi: 10.3390/cells9122653
    [9]
    Shen T, Wang W, Zhou W, et al. MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT[J]. J Clin Invest, 2021, 131(4): e135465. doi: 10.1172/JCI135465
    [10]
    Aurilio G, Cimadamore A, Mazzucchelli R, et al. Androgen receptor signaling pathway in prostate cancer: from genetics to clinical applications[J]. Cells, 2020, 9(12): 2653. doi: 10.3390/cells9122653
    [11]
    Jacob A, Raj R, Allison DB, et al. Androgen receptor signaling in prostate cancer and therapeutic strategies[J]. Cancers (Basel), 2021, 13(21): 5417. doi: 10.3390/cancers13215417
    [12]
    Di Oto E, Biserni GB, Varga Z, et al. X chromosome gain is related to increased androgen receptor expression in male breast cancer[J]. Virchows Arch, 2018, 473(2): 155-163. doi: 10.1007/s00428-018-2377-2
    [13]
    Venema CM, Bense RD, Steenbruggen TG, et al. Consideration of breast cancer subtype in targeting the androgen receptor[J]. Pharmacol Ther, 2019, 200: 135-147. doi: 10.1016/j.pharmthera.2019.05.005
    [14]
    Li Y, Xu A, Jia S, et al. Recent advances in the molecular mechanism of sex disparity in hepatocellular carcinoma[J]. Oncol Lett, 2019, 17(5): 4222-4228.
    [15]
    Han Q, Yang D, Yin C, et al. Androgen receptor (AR)-TLR4 crosstalk mediates gender disparities in hepatocellular carcinoma incidence and progression[J]. J Cancer, 2020, 11(5): 1094-1103. doi: 10.7150/jca.30682
    [16]
    Gerratana L, Basile D, Buono G, et al. Androgen receptor in triple negative breast cancer: a potential target for the targetless subtype[J]. Cancer Treat Rev, 2018, 68: 102-110. doi: 10.1016/j.ctrv.2018.06.005
    [17]
    Özturan D, Morova T, Lack NA. Androgen receptor-mediated transcription in prostate cancer[J]. Cells, 2022, 11(5): 898. doi: 10.3390/cells11050898
    [18]
    Elshan NGRD, Rettig MB, Jung ME. Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain[J]. Med Res Rev, 2019, 39(3): 910-960. doi: 10.1002/med.21548
    [19]
    Brüggenwirth HT, Boehmer AL, Verleun-Mooijman MC, et al. Molecular basis of androgen insensitivity[J]. J Steroid Biochem Mol Biol, 1996, 58(5-6): 569-575. doi: 10.1016/0960-0760(96)00095-7
    [20]
    Tan MHE, Li J, Xu HE, et al. Androgen receptor: structure, role in prostate cancer and drug discovery[J]. Acta pharmacol Sin, 2015, 36(1): 3-23. doi: 10.1038/aps.2014.18
    [21]
    Wärnmark A, Treuter E, Wright APH, et al. Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation[J]. Mol Endocrinol, 2003, 17(10): 1901-1909. doi: 10.1210/me.2002-0384
    [22]
    Yu X, Yi P, Hamilton RA, et al. Structural insights of transcriptionally active, full-length androgen receptor coactivator complexes[J]. Mol Cell, 2020, 79(5): 812-823.e4. doi: 10.1016/j.molcel.2020.06.031
    [23]
    周鑫宇, 柳东红, 蔡仕良, 等. 乙型肝炎病毒X基因及其变异促肝细胞癌的作用机制[J]. 中国癌症防治杂志, 2022, 14(1): 8-14. https://www.cnki.com.cn/Article/CJFDTOTAL-ZAZF202201017.htm

    Zhou XY, Liu DH, Cai SL, et al. The mechanism of hepatitis B virus X gene and its mutation in promoting hepatocellular carcinoma[J]. Zhongguo Ai Zheng Fang Zhi Za Zhi, 2022, 14(1): 8-14. https://www.cnki.com.cn/Article/CJFDTOTAL-ZAZF202201017.htm
    [24]
    Zhang H, Spencer K, Burley SK, et al. Toward improving androgen receptor-targeted therapies in male-dominant hepatocellular carcinoma[J]. Drug Discov Today, 2021, 26(6): 1539-1546. doi: 10.1016/j.drudis.2021.02.001
    [25]
    Ouyang X, Feng L, Liu G, et al. Androgen receptor (AR) decreases HCC cells migration and invasion via miR-325/ACP5 signaling[J]. J Cancer, 2021, 12(7): 1915-1925. doi: 10.7150/jca.49200
    [26]
    Shi L, Lin H, Li G, et al. Targeting Androgen Receptor (AR)→IL12A Signal enhances efficacy of sorafenib plus NK cells immunotherapy to better suppress HCC progression[J]. Mol Cancer Ther, 2016, 15(4): 731-742. doi: 10.1158/1535-7163.MCT-15-0706
    [27]
    Lee SR, Lee YH, Yang H, et al. Sex hormone-binding globulin suppresses NAFLD-triggered hepatocarcinogenesis after menopause[J]. Carcinogenesis, 2019, 40(8): 1031-1041. doi: 10.1093/carcin/bgz107
    [28]
    Bigsby RM, Caperell-Grant A. The role for estrogen receptor-alpha and prolactin receptor in sex-dependent DEN-induced liver tumorigenesis[J]. Carcinogenesis, 2011, 32(8): 1162-1166. doi: 10.1093/carcin/bgr094
    [29]
    Singal AG, El-Serag HB. Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice[J]. Clin Gastroenterol Hepatol, 2015, 13(12): 2140-2151. doi: 10.1016/j.cgh.2015.08.014
    [30]
    Kosinska AD, Pishraft-Sabet L, Wu W, et al. Low hepatitis B virus-specific T-cell response in males correlates with high regulatory T-cell numbers in murine models[J]. Hepatology, 2017, 66(1): 69-83. doi: 10.1002/hep.29155
    [31]
    White DL, Tavakoli-Tabasi S, Kuzniarek J, et al. Higher serum testosterone is associated with increased risk of advanced hepatitis C-related liver disease in males[J]. Hepatology, 2012, 55(3): 759-768. doi: 10.1002/hep.24618
    [32]
    Yang WJ, Chang CJ, Yeh SH, et al. Hepatitis B virus X protein enhances the transcriptional activity of the androgen receptor through c-Src and glycogen synthase kinase-3beta kinase pathways[J]. Hepatology, 2009, 49(5): 1515-1524. doi: 10.1002/hep.22833
    [33]
    Tian Y, Kuo CF, Chen WL, et al. Enhancement of hepatitis B virus replication by androgen and its receptor in mice[J]. J Virol, 2012, 86(4): 1904-1910. doi: 10.1128/JVI.06707-11
    [34]
    Tian YE, Xie XU, Lin Y, et al. Androgen receptor in hepatocarcinogenesis: recent developments and perspectives[J]. Oncol Lett, 2015, 9(5): 1983-1988. doi: 10.3892/ol.2015.3025
    [35]
    Pu R, Liu W, Zhou X, et al. The effects and underlying mechanisms of hepatitis B virus X gene mutants on the development of hepatocellular carcinoma[J]. Front Oncol, 2022, 12: 836517. doi: 10.3389/fonc.2022.836517
    [36]
    Sun H, Yang W, Tian Y, et al. An inflammatory-CCRK circuitry drives mTORC1-dependent metabolic and immunosuppressive reprogramming in obesity-associated hepatocellular carcinoma[J]. Nat Commun, 2018, 9(1): 5214. doi: 10.1038/s41467-018-07402-8
    [37]
    Lee S, Lee M, Kim JB, et al. 17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling[J]. Biochemical Biophys Res Commun, 2016, 473(4): 1247-1254. doi: 10.1016/j.bbrc.2016.04.049
    [38]
    Wu Y, Zhang Y, Qin X, et al. PI3K/AKT/mTOR pathway-related long non-coding RNAs: roles and mechanisms in hepatocellular carcinoma[J]. Pharmacol Res, 2020, 160: 105195. doi: 10.1016/j.phrs.2020.105195
    [39]
    Pungsrinont T, Kallenbach J, Baniahmad A. Role of PI3K-AKT-mTOR pathway as a pro-survival signaling and resistance-mediating mechanism to therapy of prostate cancer[J]. Int J Mol Sci, 2021, 22(20): 11088. doi: 10.3390/ijms222011088
    [40]
    Zhang H, Li XX, Yang Y, et al. Significance and mechanism of androgen receptor overexpression and androgen receptor/mechanistic target of rapamycin cross-talk in hepatocellular carcinoma[J]. Hepatology, 2018, 67(6): 2271-2286. doi: 10.1002/hep.29715
    [41]
    Tian H, Zhu X, Lv Y, et al. Glucometabolic reprogramming in the hepatocellular carcinoma microenvironment: cause and effect[J]. Cancer Manag Res, 2020, 12: 5957-5974. doi: 10.2147/CMAR.S258196
    [42]
    Ma WL, Jeng LB, Lai HC, et al. Androgen receptor enhances cell adhesion and decreases cell migration via modulating β1-integrin-AKT signaling in hepatocellular carcinoma cells[J]. Cancer Lett, 2014, 351(1): 64-71. doi: 10.1016/j.canlet.2014.05.017
    [43]
    Polivka J Jr, Janku F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway[J]. Pharmacol Ther, 2014, 142(2): 164-175. doi: 10.1016/j.pharmthera.2013.12.004
    [44]
    Shorning BY, Dass MS, Smalley MJ, et al. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling[J]. Int J Mol Sci, 2020, 21(12): 4507. doi: 10.3390/ijms21124507
    [45]
    Chen C, Wang G. Mechanisms of hepatocellular carcinoma and challenges and opportunities for molecular targeted therapy[J]. World J Hepatol, 2015, 7(15): 1964-1970. doi: 10.4254/wjh.v7.i15.1964
    [46]
    Delire B, Stärkel P. The Ras/MAPK pathway and hepatocarcinoma: pathogenesis and therapeutic implications[J]. Eur J Clin Invest, 2015, 45(6): 609-623. doi: 10.1111/eci.12441
    [47]
    Neuzillet C, Tijeras-Raballand A, De Mestier L, et al. MEK in cancer and cancer therapy[J]. Pharmacol Ther, 2014, 141(2): 160-171. doi: 10.1016/j.pharmthera.2013.10.001
    [48]
    Jin Y, Penning TM. Aldo-keto reductases and bioactivation/detoxication[J]. Annu Rev Pharmacol Toxicol, 2007, 47: 263-292. doi: 10.1146/annurev.pharmtox.47.120505.105337
    [49]
    Penning TM. Aldo-Keto Reductase (AKR) 1C3 inhibitors: a patent review[J]. Expert Opin Ther Pat, 2017, 27(12): 1329-1340. doi: 10.1080/13543776.2017.1379503
    [50]
    Jansson AK, Gunnarsson C, Cohen M, et al. 17beta-hydroxysteroid dehydrogenase 14 affects estradiol levels in breast cancer cells and is a prognostic marker in estrogen receptor-positive breast cancer[J]. Cancer Res, 2006, 66(23): 11471-11477. doi: 10.1158/0008-5472.CAN-06-1448
    [51]
    Wang B, Gu Y, Hui K, et al. AKR1C3, a crucial androgenic enzyme in prostate cancer, promotes epithelial-mesenchymal transition and metastasis through activating ERK signaling[J]. Urol Oncol, 2018, 36(10): 472.e11-e472.e20. doi: 10.1016/j.urolonc.2018.07.005
    [52]
    Zhu P, Feng R, Lu X, et al. Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma[J]. Aging (Albany NY), 2021, 13(3): 4138-4156.
    [53]
    Song H, Yu Z, Sun X, et al. Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/β-catenin signaling[J]. EBioMedicine, 2018, 35: 155-166. doi: 10.1016/j.ebiom.2018.08.043
    [54]
    Feng H, Yu Z, Tian Y, et al. A CCRK-EZH2 epigenetic circuitry drives hepatocarcinogenesis and associates with tumor recurrence and poor survival of patients[J]. J Hepatol, 2015, 62(5): 1100-1111. doi: 10.1016/j.jhep.2014.11.040
    [55]
    Wei Y, Renard CA, Labalette C, et al. Identification of the LIM protein FHL2 as a coactivator of beta-catenin[J]. J Biol Chem, 2003, 278(7): 5188-5194. doi: 10.1074/jbc.M207216200
    [56]
    Tong Z, Li M, Wang W, et al. Steroid receptor coactivator 1 promotes human hepatocellular carcinoma progression by enhancing Wnt/β-Catenin signaling[J]. J Biol Chem, 2015, 290(30): 18596-18608. doi: 10.1074/jbc.M115.640490
    [57]
    Xu J, Zheng L, Chen J, et al. Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals[J]. Cell Death Dis, 2017, 8(10): e3095. doi: 10.1038/cddis.2017.411
    [58]
    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4): 378-390. doi: 10.1056/NEJMoa0708857
    [59]
    Kanda T, Yokosuka O. The androgen receptor as an emerging target in hepatocellular carcinoma[J]. J Hepatocell Carcinoma, 2015, 2: 91-99.
    [60]
    Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. Randomized trial of leuprorelin and flutamide in male patients with hepatocellular carcinoma treated with tamoxifen[J]. Hepatology, 2004, 40(6): 1361-1369. doi: 10.1002/hep.20474
    [61]
    Wang SH, Yeh SH, Shiau CW, et al. Sorafenib action in hepatitis B virus X-activated oncogenic androgen pathway in liver through SHP-1[J]. J Natl Cancer Inst, 2015, 107(10): djv190. doi: 10.1093/jnci/djv190
    • Related Articles

  • Related Articles

    [1]YANG Yijie, WANG Shuai, XU Xiao. Research Progress on Cancer-Associated Fibroblasts in Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2024, 51(7): 527-534. DOI: 10.3971/j.issn.1000-8578.2024.24.0146
    [2]CAO Jiali, XIONG Zhifan, JIN Ze, MENG Yajun, HUANG Yumei, ZHU Mengpei, WANG Mengmeng. Research Progress on Immune Checkpoint Inhibitors in Treatment of Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2023, 50(5): 525-530. DOI: 10.3971/j.issn.1000-8578.2023.22.1325
    [3]WANG Zihe, LI Zengliang, FANG Xuzhe, ZHU Jin. Research Progress on Influence of DNA Methylation on Signal Pathways Related to Invasion and Metastasis of Nasopharyngeal Carcinoma[J]. Cancer Research on Prevention and Treatment, 2022, 49(9): 956-960. DOI: 10.3971/j.issn.1000-8578.2022.22.0052
    [4]ZHOU Silei, SUN Guanqun, ZENG Tanlun, CHENG Zhuo, LIANG Xijun. Expression and Prognostic Value of CK2α' in Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2022, 49(7): 662-666. DOI: 10.3971/j.issn.1000-8578.2022.21.1291
    [5]WANG Jue, JIN Zongrui, WANG Wei, YI Qilin, WANG Jilong, ZHU Hai, XU Banghao, GUO Ya, WEN Zhang. Prognostic Role of Immune-related Genes in Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2022, 49(6): 599-605. DOI: 10.3971/j.issn.1000-8578.2022.21.1240
    [6]SHAO Lihua, ZHANG Qiuning, LUO Hongtao, YANG Zhen, LIU Ruifeng, TIAN Jinhui, LI Zheng, WANG Xiaohu, YANG Kehu. Carbonions and Proton Therapy for Hepatocellular Carcinoma: A Meta-analysis[J]. Cancer Research on Prevention and Treatment, 2020, 47(5): 358-366. DOI: 10.3971/j.issn.1000-8578.2020.19.1158
    [7]ZHANG Tingting, WANG Xiangyi, GUO Ziwei, DING Xiaosheng, LIANG Jun. Prognostic Significance of Platelet-lymphocyte Ratio in Hepatocellular Carcinoma Patients: A Meta-analysis[J]. Cancer Research on Prevention and Treatment, 2018, 45(10): 775-780. DOI: 10.3971/j.issn.1000-8578.2018.18.0151
    [8]LU Xianzhou, LIU Longfei, ZHOU Xiaojun, XIAO Shuai, LONG Jianwu, ZHOU Xian. GPR124 Expression and Its Relationship with Prognosis in Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2014, 41(10): 1082-1086. DOI: 10.3971/j.issn.1000-8578.2014.10.006
    [9]HU Rong-huan, LIU An-wen, CAI Jing, ZHANG Shu-hui. Expression and Significance of MAP4K4 in Hepatocellular Carcinoma[J]. Cancer Research on Prevention and Treatment, 2011, 38(07): 752-755. DOI: 10.3971/j.issn.1000-8578.2011.07.006
    [10]YANG Zhi-fang, YI Ji-lin, LI Xing-rui, LONG Wei. Expression of PTEN in Hepatocellular Carcinoma and Its Correlation with Phosphorylation of PKB/AKT[J]. Cancer Research on Prevention and Treatment, 2004, 31(12): 748-750. DOI: 10.3971/j.issn.1000-8578.1588

  • Cited by

    Periodical cited type(1)

    1. 顾庆龙，王依晖，刘曙亮. 原发性肺脂肪肉瘤1例并文献复习. 肿瘤研究与临床. 2024(10): 784-786 .

    Other cited types(0)

Catalog

    Get Citation
    PDF
    XML
    Article views (2116) PDF downloads (2066) Cited by(1)
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Contact Us

    Address：116 Zhuodaoquan South Road,
    Hongshan District, Wuhan（430079）

    Tel：027－87670126

    Email：zlfzyjzz@vip.163.com

    This work is licensed under a Creative Commons Attribution 3.0 License.

    Email Alert RSS
    Total visits：18986991 Visits today：14539

    Copyright © Editorial Department of Cancer Prevention Research 鄂公网安备 42011102005013号 鄂ICP备2022015867号

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return