A Tumor Suppressor Locus Within 3p14-p12 Mediates Rapid Cell Death of Renal Cell Carcinoma in Vivo

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Apr 12

PMID 8159756

Citations 18

Authors

Y Sanchez

A El-Naggar

S Pathak

A M Killary

Affiliations

Soon will be listed here.

Abstract

High frequency loss of alleles and cytogenetic aberrations on the short arm of chromosome 3 have been documented in renal cell carcinoma (RCC). Potentially, three distinct regions on 3p could encode tumor suppressor genes involved in the genesis of this cancer. We report that the introduction of a centric fragment of 3p, encompassing 3p14-q11, into a highly malignant RCC cell line resulted in a dramatic suppression of tumor growth in athymic nude mice. Another defined deletion hybrid contained the region 3p12-q24 of the introduced human chromosome and failed to suppress tumorigenicity. These data functionally define a tumor suppressor locus, nonpapillary renal carcinoma-1 (NRC-1), within 3p14-p12, the most proximal region of high frequency allele loss in sporadic RCC as well as the region containing the translocation breakpoint in familial RCC. Furthermore, we provide functional evidence that NRC-1 controls the growth of RCC cells by inducing rapid cell death in vivo.

Citing Articles

Modeling clear cell renal cell carcinoma and therapeutic implications.

Wolf M, Rathmell W, Beckermann K Oncogene. 2020; 39(17):3413-3426.

PMID: 32123314 PMC: 7194123. DOI: 10.1038/s41388-020-1234-3.

Identification of genetic variants predictive of early onset pancreatic cancer through a population science analysis of functional genomic datasets.

Chen J, Wu X, Huang Y, Chen W, Brand R, Killary A Oncotarget. 2016; 7(35):56480-56490.

PMID: 27486767 PMC: 5302929. DOI: 10.18632/oncotarget.10924.

DEAR1, a novel tumor suppressor that regulates cell polarity and epithelial plasticity.

Chen N, Balasenthil S, Reuther J, Killary A Cancer Res. 2014; 74(20):5683-9.

PMID: 25261235 PMC: 4214267. DOI: 10.1158/0008-5472.CAN-14-1171.

VGLL3 expression is associated with a tumor suppressor phenotype in epithelial ovarian cancer.

Gambaro K, Quinn M, Wojnarowicz P, Arcand S, de Ladurantaye M, Barres V Mol Oncol. 2013; 7(3):513-30.

PMID: 23415753 PMC: 5528482. DOI: 10.1016/j.molonc.2012.12.006.

Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer.

Dovzhanskiy D, Arnold S, Hackert T, Oehme I, Witt O, Felix K BMC Cancer. 2012; 12:226.

PMID: 22681698 PMC: 3407493. DOI: 10.1186/1471-2407-12-226.

References

Shimizu M, Yokota J, Mori N, Shuin T, Shinoda M, Terada M . Introduction of normal chromosome 3p modulates the tumorigenicity of a human renal cell carcinoma cell line YCR. Oncogene. 1990; 5(2):185-94. View

Latif F, Tory K, Gnarra J, Yao M, Duh F, Orcutt M . Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993; 260(5112):1317-20. DOI: 10.1126/science.8493574. View

Ogawa O, Kakehi Y, Ogawa K, Koshiba M, Sugiyama T, Yoshida O . Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma. Cancer Res. 1991; 51(3):949-53. View

Southern E . Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975; 98(3):503-17. DOI: 10.1016/s0022-2836(75)80083-0. View

Cohen A, Li F, Berg S, Marchetto D, Tsai S, Jacobs S . Hereditary renal-cell carcinoma associated with a chromosomal translocation. N Engl J Med. 1979; 301(11):592-5. DOI: 10.1056/NEJM197909133011107. View

McNeill C, Brown R . Genetic manipulation by means of microcell-mediated transfer of normal human chromosomes into recipient mouse cells. Proc Natl Acad Sci U S A. 1980; 77(9):5394-8. PMC: 350065. DOI: 10.1073/pnas.77.9.5394. View

Stanbridge E, Ceredig R . Growth-regulatory control of human cell hybrids in nude mice. Cancer Res. 1981; 41(2):573-80. View

Fournier R . A general high-efficiency procedure for production of microcell hybrids. Proc Natl Acad Sci U S A. 1981; 78(10):6349-53. PMC: 349036. DOI: 10.1073/pnas.78.10.6349. View

Pathak S, Strong L, Ferrell R, Trindade A . Familial renal cell carcinoma with a 3;11 chromosome translocation limited to tumor cells. Science. 1982; 217(4563):939-41. DOI: 10.1126/science.7112106. View

10.

Gerber M, Miller Y, Drabkin H, Scoggin C . Regional assignment of the polymorphic probe D3S3 to 3p14 by molecular hybridization. Cytogenet Cell Genet. 1986; 42(1-2):72-4. DOI: 10.1159/000132254. View

11.

Naito S, Von Eschenbach A, Giavazzi R, Fidler I . Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 1986; 46(8):4109-15. View

12.

Saxon P, Srivatsan E, Stanbridge E . Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. EMBO J. 1986; 5(13):3461-6. PMC: 1167381. DOI: 10.1002/j.1460-2075.1986.tb04670.x. View

13.

Weissman B, Saxon P, Pasquale S, Jones G, Geiser A, Stanbridge E . Introduction of a normal human chromosome 11 into a Wilms' tumor cell line controls its tumorigenic expression. Science. 1987; 236(4798):175-80. DOI: 10.1126/science.3031816. View

14.

Carroll P, Murty V, Reuter V, Jhanwar S, Fair W, Whitmore W . Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma. Cancer Genet Cytogenet. 1987; 26(2):253-9. DOI: 10.1016/0165-4608(87)90059-8. View

15.

Zbar B, Brauch H, Talmadge C, Linehan M . Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature. 1987; 327(6124):721-4. DOI: 10.1038/327721a0. View

16.

Osborne C, Coronado E, Robinson J . Human breast cancer in the athymic nude mouse: cytostatic effects of long-term antiestrogen therapy. Eur J Cancer Clin Oncol. 1987; 23(8):1189-96. DOI: 10.1016/0277-5379(87)90154-4. View

17.

Kovacs G, Erlandsson R, Boldog F, Ingvarsson S, Klein G, Sumegi J . Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci U S A. 1988; 85(5):1571-5. PMC: 279815. DOI: 10.1073/pnas.85.5.1571. View

18.

Bergerheim U, Nordenskjold M, Collins V . Deletion mapping in human renal cell carcinoma. Cancer Res. 1989; 49(6):1390-6. View

19.

Kovacs G, Brusa P, de Riese W . Tissue-specific expression of a constitutional 3;6 translocation: development of multiple bilateral renal-cell carcinomas. Int J Cancer. 1989; 43(3):422-7. DOI: 10.1002/ijc.2910430313. View

20.

Tory K, Brauch H, Linehan M, Barba D, Oldfield E, Seizinger B . Specific genetic change in tumors associated with von Hippel-Lindau disease. J Natl Cancer Inst. 1989; 81(14):1097-101. DOI: 10.1093/jnci/81.14.1097. View