Abstract
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 glycinerich 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.
Similar content being viewed by others
References
Jemal A, Thomas A, Murray T, Thun M. (2002) Cancer statistics, 2002. Cancer J. Clin. 52: 23–47.
Cabeza-Arvelaiz Y, Sepulveda JL, Lebovitz RM, Thompson TC, Chinault AC. (2001) Functional identification of LZTS1 as a candidate prostate tumor suppressor gene on human chromosome 8p22. Oncogene 20: 4169–4179.
Baffa R, Santoro R, Bullrich F, Mandes B, Ishii H, Croce CM. (2000) Definition and refinement of chromosome 8p regions of loss of heterozygosity in gastric cancer. Clin. Cancer Res. 6: 1372–1377.
Sato K, Qian J, Slezak JM, et al. (1999) Clinical significance of alterations of chromosome 8 in high-grade, advanced, non-metastatic prostate carcinoma. J. Natl. Cancer Inst. 91: 1574–1580.
Dahiya R, Perinchery G, Deng G, Lee C. (1998) Multiple sites of loss of heterozygosity on chromosome 8 in human breast cancer has differential correlation with clinical parameters. Int. J. Oncol. 12: 811–816.
Voeller HJ, Augustus M, Madike V, Bova GS, Carter KC, Gelmann EP. (1997) Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers. Cancer Res. 57: 4455–4459.
Yaremko ML, Kutza C, Lyzak J, Mick R, Recant WM, Westbrook CA. (1996) Loss of heterozygosity from the short arm of chromosome 8 is associated with invasive behavior in breast cancer. Genes Chromosomes Cancer 16: 189–195.
Li J, Yen C, Liaw D, et al. (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943–1947.
Suzuki H, Freije D, Nusskern DR, et al. (1998) Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res. 58: 204–209.
Zenklusen JC, Conti CJ, Green ED. (2001) Mutational and functional analyses reveal that ST7 is a highly conserved tumor-suppressor gene on human chromosome 7q31. Nat. Genet. 27: 392–398.
Narla G, Heath KE, Reeves HL, et al. (2001) KLF6, a candidate tumor suppressor gene mutated in prostate cancer. Science 294: 2563–2566.
Reiter RE, Sato I, Thomas G, et al. (2000) Coamplification of prostate stem cell antigen (PSCA) and MYC in locally advanced prostate cancer. Genes Chromosomes Cancer 27: 95–103.
Cher ML, Bova GS, Moore DH, et al. (1996) Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping. Cancer Res. 56: 3091–3102.
Sun M, Ma L, Li J, et al. (2002) Characterization of a novel tumor suppressor gene locus on chromosome 6q16.1 in prostate cancer. Proceedings of the American Association for Cancer Research 43: 630.
Cussenot O, Valeri A, Berthon P, Fournier G, Mangin P. (1998) Hereditary prostate cancer and other genetic predispositions to prostate cancer. Urol. Int. 60(suppl 2): 30–34.
Isaacs WB. (1995) Molecular genetics of prostate cancer. Cancer Surv. 25: 357–379.
Tavtigian SV, Simard J, Teng DH, et al. (2001) A candidate prostate cancer susceptibility gene at chromosome 17p. Nat. Genet. 27: 172–180.
Carpten J, Nupponen N, Isaacs S, et al. (2002) Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat. Genet. 30: 181–184.
Rokman A, Ikonen T, Seppala EH, et al. (2002) Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. Am. J. Hum. Genet. 70: 1299–1304.
Latil A, Cussenot O, Fournier G, Driouch K, Lidereau R. (1997) Loss of heterozygosity at chromosome 16q in prostate adenocarcinoma: identification of three independent regions. Cancer Res. 57: 1058–1062.
Li C, Berx G, Larsson C, et al. (1999) Distinct deleted regions on chromosome segment 16q23–24 associated with metastases in prostate cancer. Genes Chromosomes Cancer 24: 175–182.
Hainsworth PJ, Raphael KL, Stillwell RG, Bennett RC, Garson OM. (1991) Cytogenetic features of twenty-six primary breast cancers. Cancer Genet. Cytogenet. 53: 205–218.
Callen DF, Crawford J, Derwas C, Cleton-Jansen AM, Cornelisse CJ, Baker E. (2002) Defining regions of loss of heterozygosity of 16q in breast cancer cell lines. Cancer Genet. Cytogenet. 133: 76–82.
Dome JS, Coppes MJ. (2002) Recent advances in Wilms tumor genetics. Curr. Opin. Pediatr. 14: 5–11.
Guan XY, Fang Y, Sham JS, et al. (2000) Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer. 29: 110–116.
Horwitz M, Benson KF, Li FQ, et al. (1997) Genetic heterogeneity in familial acute myelogenous leukemia: evidence for a second locus at chromosome 16q21–23.2. Am. J. Hum. Genet. 61: 873–881.
Paris PL, Witte JS, Kupelian PA, et al. (2000) Identification and fine mapping of a region showing a high frequency of allelic imbalance on chromosome 16q23.2 that corresponds to a prostate cancer susceptibility locus. Cancer Res. 60: 3645–3649.
Ikonen T, Matikainen M, Mononen N, et al. (2001) Association of E-cadherin germ-line alterations with prostate cancer. Clin. Cancer Res. 7: 3465–3471.
Graff JR, Herman JG, Lapidus RG, et al. (1995) E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res. 55: 5195–5199.
Corn PG, Smith BD, Ruckdeschel ES, Douglas D, Baylin SB, Herman JG. (2000) E-cadherin expression is silenced by 5′ CpG island methylation in acute leukemia. Clin. Cancer Res. 6: 4243–4248.
Xu LL, Su YP, Labiche R, et al. (2001) Quantitative expression profile of androgen-regulated genes in prostate cancer cells and identification of prostate-specific genes. Int. J. Cancer 92: 322–328.
Umbas R, Isaacs WB, Bringuier PP, et al. (1994) Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 54: 3929–3933.
Luo J, Zha S, Gage WR, et al. (2002) Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer. Cancer Res. 62: 2220–2226.
Rubin MA, Zhou M, Dhanasekaran SM, et al. (2002) alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA 287: 1662–1670.
de Kok JB, Verhaegh GW, Roelofs RW, et al. (2002) DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 62: 2695–2698.
Bickmore WA, Sutherland HGE. (2002) Addressing protein localization within the nucleus. EMBO J. 21: 1248–1254.
Feller SM, Ren R, Hanufusa H, Baltimore D. (1994) SH2 and SH3 domains as molecular adhesives: the interactions of Crk and Abl. Trends Biochem. Sci. 19: 453–458.
Cohen GB, Ren R, Baltimore D. (1995) Modular binding domains in signal transduction proteins. Cell 80: 237–248.
Schlessinger J. (1994) SH2/SH3 signaling proteins. Curr. Opin. Genet. Dev. 4: 25–30.
Birge RB, Knudsen BS, Besser D, Hanafusa H. (1996) SH2 and SH3-containing adaptor proteins: redundant or independent mediators of intracellular signal transduction. Genes Cells 1: 595–613.
Acknowledgments
We thank Ms Justine Cowan for her critical reading of the manuscript. This work was supported by the Center for Prostate Disease Research, a program of the Henry M. Jackson Foundation for the Advancement of Military Medicine (Rockville, MD), funded by the United States Army Medical Research and Material Command.
The author is supported by a grant from the Center for Prostate Disease Research, a program of the Henry M. Jackson Foundation for the Advancement of Military Medicine (Rockville, MD), funded by the U.S. Army Medical Research and Materiel Command.
Author information
Authors and Affiliations
Corresponding author
Additional information
The opinions and assertions contained herein are the private views of the authors and are not to be considered as reflecting the views of the U.S. Army or the Department of Defense.
Rights and permissions
About this article
Cite this article
Sun, M., Ma, L., Xu, L. et al. A Human Novel Gene DERPC Located on 16q22.1 Inhibits Prostate Tumor Cell Growth and Its Expression Is Decreased in Prostate and Renal Tumors. Mol Med 8, 655–663 (2002). https://doi.org/10.1007/BF03402176
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03402176