Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2.
Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor, which has previously been shown to be expressed in a variety of cancers. HDGF overexpression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is overexpressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1, and PC-3 cells. Forced overexpression enhanced cell viability of RWPE-1 cells, whereas HDGF knockdown reduced cell proliferation in human prostate cancer cells. We also show that HDGF may serve as a survival-related protein as ectopic overexpression of HDGF in RWPE cells up-regulated the expression of antiapoptosis proteins cyclin E and BCL-2, whereas simultaneously down-regulating proapoptotic protein BAX. Western blot analysis also showed that HDGF overexpression modulated the activity of phospho-AKT as well as NF-kB, and these results correlated with in vitro migration and invasion assays. We next assessed the therapeutic potential of HDGF inhibition with a HDGF monoclonal antibody and vitamin k2, showing reduced cell proliferation as well as inhibition of NF-kB expression in HDGF overexpressed RWPE cells treated with a HDGF monoclonal antibody and vitamin K2. Collectively, our results suggest that HDGF is a relevant protein in prostate oncogenesis and may serve as a potential therapeutic target in prostate cancer.
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL.
Aditya
A
Shetty
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL.
Subramanyam
S
Dasari
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL.
Souresh
S
Banerjee
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL.
Taher
T
Gheewala
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL.
Guoxing
G
Zheng
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL.
Aoshuang
A
Chen
Department of Pathology, University of Illinois at Chicago, Chicago, IL.
Andre
A
Kajdacsy-Balla
Department of Pathology, University of Illinois at Chicago, Chicago, IL.
Maarten C
MC
Bosland
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL. Electronic address: mgnanas@uic.edu.
Gnanasekar
G
Munirathinam
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000728:Androgens; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D024482:Vitamin K 2 / Q000494:pharmacology
D000728:Androgens; D000911:Antibodies, Monoclonal; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C051610:hepatoma-derived growth factor; D024482:Vitamin K 2
AKT; HDGF; Invasion; Migration; NF-kB; Proliferation; Vitamin K2
Oncol Res. 2010;19(2):67-76
21302807
Int J Oncol. 2011 Sep;39(3):635-40
21637916
J Clin Invest. 2000 Mar;105(5):567-75
10712428
Tumour Biol. 2014 Sep;35(9):8861-6
24891187
Mol Cancer Ther. 2009 May;8(5):1106-12
19435872
Clin Cancer Res. 2006 Jan 1;12(1):117-22
16397032
J Clin Oncol. 2004 Aug 15;22(16):3230-7
15310766
Cancer Res. 2003 Oct 15;63(20):6716-25
14583466
Clin Cancer Res. 2013 Jul 1;19(13):3567-76
23695169
Mol Cell Biochem. 2014 Mar;388(1-2):211-8
24276755
Cell. 2011 Mar 4;144(5):646-74
21376230
Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6043-8
17062679
Apoptosis. 2008 Sep;13(9):1135-47
18651222
J Clin Invest. 1998 Sep 15;102(6):1208-19
9739055
Cancer Res. 2006 Jan 1;66(1):18-23
16397209
Cancer. 2003 Oct 1;98(7):1444-56
14508832
Int J Cancer. 2007 Oct 1;121(7):1424-32
17551921
PLoS One. 2013;8(3):e59345
23536873
J Biol Chem. 1994 Oct 7;269(40):25143-9
7929202
J Cell Biochem. 2004 Jan 1;91(1):100-17
14689584
Cell. 1997 Oct 17;91(2):231-41
9346240
Hepatogastroenterology. 2002 Nov-Dec;49(48):1639-44
12397753
CA Cancer J Clin. 2013 Jan;63(1):11-30
23335087
Am J Pathol. 2009 Aug;175(2):489-99
19628766
Acta Biochim Biophys Sin (Shanghai). 2010 Jan;42(1):52-7
20043047
Oncogene. 2001 Jul 12;20(31):4188-97
11464285
BMC Cancer. 2010 Jun 16;10:294
20553606
Endocr Relat Cancer. 2013 May 20;20(3):R83-99
23456430
Cell. 1999 Mar 19;96(6):857-68
10102273
J Hepatol. 2012 Sep;57(3):584-91
22613005
Stem Cells. 2012 May;30(5):845-53
22331796
J Gastroenterol. 2009;44(3):228-35
19214667