A human novel gene DERPC located on 16q22.1 inhibits prostate tumor cell growth and its expression is decreased in prostate and renal tumors

被引:13
作者
Sun, M
Ma, LF
Xu, LD
Li, J
Zhang, W
Petrovics, G
Makarem, M
Sesterhenn, I
Zhang, M
Blanchette-Mackie, EJ
Moul, J
Srivastava, S
Zou, ZQ
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Rockville, MD 20852 USA
[2] Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC USA
[3] NIH, NIDDKD, Lab Cell Biochem & Biol, Sect Lipid Cell Biol, Bethesda, MD USA
[4] Walter Reed Army Med Ctr, Dept Surg, Serv Urol, Washington, DC USA
关键词
D O I
10.1007/BF03402176
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Deletion of chromosome 16q is frequently associated with diverse tumors. Numerous studies strongly suggest the presence of one or more tumor suppressor genes on chromosome 16q22 to 16qter including the widely studied cadherin gene family. However, the specific tumor suppressor genes residing in this region need better definition and characterization. Material and Methods: Standard molecular biology approaches have been used to clone and characterize the DERPC cDNA and its protein product on chromosome 16q22.1. Northern blotting was used to define the expression pattern in a multiple human tissue blots. DERPC expression was examined in multi-tumor array (Clontech, CA, USA) dot blot as well as in laser capture microdissection (LCM) derived prostate cancer (CaP) specimens by quantitative RT-PCR. Western blot analysis and a fluorescent microscopy were used to characterize the molecular size and the cellular location of green fluorescent protein (GFP)-tagged DERPC fusion proteins. A colony formation assay was conducted to determine the effects of DERPC expression on tumor cell growth. Results: A novel gene DERPC (Decreased Expression in Renal and Prostate Cancer) was identified and characterized. DERPC encoded a strong basic, proline- and glycine-rich nuclear protein. DERPC was ubiquitously expressed, with abundant expression in kidney, skeletal muscle, testis, liver, ovary, and heart and moderate expression in prostate. DERPC expression was reduced in renal (67%) and prostate tumors (33%). Expression of DERPC has inhibitory potential on CaP cell growth. Further, overexpression of DERPC in LNCaP cells caused alterations of nuclear morphology. Conclusion: This study suggests that decreased expression of DERPC may be implicated in tumorigenesis of renal and CaPs.
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页码:655 / 663
页数:9
相关论文
共 43 条
[1]  
Baffa R, 2000, CLIN CANCER RES, V6, P1372
[2]   Addressing protein localization within the nucleus [J].
Bickmore, WA ;
Sutherland, HGE .
EMBO JOURNAL, 2002, 21 (06) :1248-1254
[3]   SH2 and SH3-containing adaptor proteins: Redundant or Independent mediators of intracellular signal transduction [J].
Birge, RB ;
Knudsen, BS ;
Besser, D ;
Hanafusa, H .
GENES TO CELLS, 1996, 1 (07) :595-613
[4]   Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22 [J].
Cabeza-Arvelaiz, Y ;
Sepulveda, JL ;
Lebovitz, RM ;
Thompson, TC ;
Chinault, AC .
ONCOGENE, 2001, 20 (31) :4169-4179
[5]   Defining regions of loss of heterozygosity of 16q in breast cancer cell lines [J].
Callen, DF ;
Crawford, J ;
Derwas, C ;
Cleton-Jansen, AM ;
Cornelisse, CJ ;
Baker, E .
CANCER GENETICS AND CYTOGENETICS, 2002, 133 (01) :76-82
[6]   Germline mutations in the ribonuclease L gene in families showing linkage with HPC1 [J].
Carpten, J ;
Nupponen, N ;
Isaacs, S ;
Sood, R ;
Robbins, C ;
Xu, J ;
Faruque, M ;
Moses, T ;
Ewing, C ;
Gillanders, E ;
Hu, P ;
Buinovszky, P ;
Makalowska, I ;
Baffoe-Bonnie, A ;
Faith, D ;
Smith, J ;
Stephan, D ;
Wiley, K ;
Brownstein, M ;
Gildea, D ;
Kelly, B ;
Jenkins, R ;
Hostetter, G ;
Matikainen, M ;
Schleutker, J ;
Klinger, K ;
Connors, T ;
Xiang, Y ;
Wang, Z ;
De Marzo, A ;
Papadopoulos, N ;
Kallioniemi, OP ;
Burk, R ;
Meyers, D ;
Grönberg, H ;
Meltzer, P ;
Silverman, R ;
Bailey-Wilson, J ;
Walsh, P ;
Isaacs, W ;
Trent, J .
NATURE GENETICS, 2002, 30 (02) :181-184
[7]  
Cher ML, 1996, CANCER RES, V56, P3091
[8]   MODULAR BINDING DOMAINS IN SIGNAL-TRANSDUCTION PROTEINS [J].
COHEN, GB ;
REN, RB ;
BALTIMORE, D .
CELL, 1995, 80 (02) :237-248
[9]  
Corn PG, 2000, CLIN CANCER RES, V6, P4243
[10]   Hereditary prostate cancer and other genetic predispositions to prostate cancer [J].
Cussenot, O ;
Valeri, A ;
Berthon, P ;
Fournier, G ;
Mangin, P .
UROLOGIA INTERNATIONALIS, 1998, 60 :30-34