title: RTN4IP1 is down-regulated in thyroid cancer and has tumor-suppressive function.
abstract: BACKGROUND
  Previously we identified RTN4IP1 to be differentially expressed in thyroid cancer by sex and the gene is located on chromosome 6q21, a chromosomal region frequently deleted or with loss of heterozygosity in a variety of human malignancies including thyroid cancer.
  
  
  OBJECTIVE
  Because the expression and function of this gene is unknown, we sought to characterize its expression in normal, hyperplastic, and benign and malignant thyroid tissue samples and to evaluate its function in cancer cells.
  
  
  METHODS
  RTN4IP1 expression was analyzed in normal and hyperplastic thyroid tissue and benign and malignant thyroid tissue samples. In 3 thyroid cancer cell lines (TPC1 from a papillary thyroid cancer, FTC133 from a follicular thyroid cancer, XTC1 from a Hürthle cell carcinoma), small interfering RNA knockdown of RTN4IP1 was used to determine its role in regulating the hallmarks of malignant cell phenotype (cellular proliferation, migration, apoptosis, invasion, tumor spheroid formation, anchorage independent growth).
  
  
  RESULTS
  We found RTN4IP1 mRNA expression was significantly down-regulated in follicular and papillary thyroid cancer as compared with normal, hyperplastic, and benign thyroid neoplasms (P < .05). Moreover, RTN4IP1 mRNA expression was significantly lower in larger papillary thyroid cancers (P < .05). Small interfering RNA knockdown of RTN4IP1 expression increased cellular proliferation (2- to 4-fold) in all 3 of the cell lines tested and increased cellular invasion (1.5- to 3-fold) and migration (2- to 7.5-fold), colony formation (3- to 6-fold), and tumor spheroid formation (P < .05) in 2 of the 3 cell lines tested (FTC-133 and XTC1).
  
  
  CONCLUSIONS
  This is the first study to characterize the expression and function of RTN4IP1 in cancer. Our results demonstrate RTN4IP1 is down-regulated in thyroid cancer and is associated with larger papillary thyroid cancer and that it regulates malignant cell phenotype. These findings, taken together, suggest that RTN4IP1 has a tumor-suppressive function and may regulate thyroid cancer progression.
authors: Endocrine Oncology Branch, Clinical Research Center, 10 Center Drive, MSC 1201, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors: Reza
authors: R
authors: Rahbari
authors: Mio
authors: M
authors: Kitano
authors: Lisa
authors: L
authors: Zhang
authors: Swaroop
authors: S
authors: Bommareddi
authors: Electron
authors: E
authors: Kebebew
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D018249:Adenoma, Oxyphilic; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D002352:Carrier Proteins / Q000235:genetics*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C459094:RTN4IP1 protein, human
references: Trends Cell Biol. 2003 Apr;13(4):187-94
references: 12667756
references: Mol Carcinog. 2001 Jul;31(3):161-70
references: 11479925
references: Cell. 2005 Jun 17;121(6):837-48
references: 15960972
references: Cold Spring Harb Symp Quant Biol. 2005;70:363-74
references: 16869773
references: Am J Pathol. 2002 Nov;161(5):1549-56
references: 12414503
references: Endocr Relat Cancer. 2011 Nov 28;18(6):731-42
references: 21990323
references: Cancer Res. 1991 Dec 1;51(23 Pt 1):6338-45
references: 1933896
references: Apoptosis. 2003 Jan;8(1):5-9
references: 12510146
references: J Clin Oncol. 1998 Oct;16(10):3286-94
references: 9779703
references: Development. 1997 May;124(10):1953-62
references: 9169842
references: Cell Cycle. 2006 Sep;5(17):1929-35
references: 16929174
references: Nat Rev Neurosci. 2010 Dec;11(12):799-811
references: 21045861
references: Cancer Res. 2002 Dec 1;62(23):7004-11
references: 12460920
references: J Pathol. 2002 Jan;196(1):8-16
references: 11748636
references: Blood. 2011 Feb 17;117(7):2284-95
references: 21183689
references: Int J Biochem Cell Biol. 2007;39(5):874-8
references: 17137827
references: Cancer. 2009 Aug 15;115(16):3801-7
references: 19598221
references: Genes Chromosomes Cancer. 2000 Jan;27(1):52-8
references: 10564586
references: JAMA. 2006 May 10;295(18):2164-7
references: 16684987
references: Curr Opin Oncol. 2008 Jan;20(1):13-8
references: 18043251
references: Blood. 1996 Aug 15;88(4):1418-22
references: 8695862
references: Clin Endocrinol (Oxf). 2006 Oct;65(4):500-5
references: 16984243
references: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16789-94
references: 21921234
references: Respir Res. 2011 Jan 21;12:14
references: 21251247
references: Oncogene. 2001 Jul 5;20(30):3929-36
references: 11494121
references: J Clin Endocrinol Metab. 2005 Dec;90(12):6373-9
references: 16174717
references: Mol Ther. 2008 Nov;16(11):1798-804
references: 18781142
references: Int J Cancer. 2000 May 15;86(4):524-8
references: 10797266
references: Clin Cancer Res. 1996 Sep;2(9):1601-6
references: 9816339
references: Neurosci Bull. 2006 May;22(3):183-6
references: 17704847
references: Cancer. 2011 Oct 1;117(19):4390-5
references: 21412762
references: Carcinogenesis. 2007 Apr;28(4):777-84
references: 17088259
references: Future Oncol. 2010 Nov;6(11):1771-9
references: 21142662
references: Ann Surg. 2007 Sep;246(3):466-70; discussion 470-1
references: 17717450
references: J Neurochem. 2002 Apr;81(1):36-45
references: 12067236