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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2002 Jun;93(6):605–609. doi: 10.1111/j.1349-7006.2002.tb01297.x

Promoter Methylation of TSLC1 and Tumor Suppression by Its Gene Product in Human Prostate Cancer

Hiroshi Fukuhara 1, Masami Kuramochi 1, Takeshi Fukami 1, Kohtaro Kasahara 2, Mutsuo Furuhata 3, Takahiro Nobukuni 1, Tomoko Maruyama 1, Kana Isogai 1, Takao Sekiya 1, Taro Shuin 2, Tadaichi Kitamura 4, Roger H Reeves 5, Yoshinori Murakami 1,
PMCID: PMC5927049  PMID: 12079507

Abstract

We recently identified TSLC1, a tumor suppressor gene in human lung cancer. Gene silencing by promoter methylation has been observed frequently in adenocarcinoma of the lung, liver, and pancreas. Here, we demonstrate that TSLC1 expression is also absent or markedly reduced in 3 of 4 prostate cancer cell lines. Promoter sequences of TSLC1 were heavily methylated in PPC‐1 cells that lacked TSLC1 expression, supporting the idea that promoter methylation is strongly correlated with complete loss of gene expression. Promoter sequences of TSLC1 were also methylated significantly in 7 of 22 (32%) primary prostate cancers. Hypermethylation of the promoter occurred not only in advanced tumors, but also in relatively early‐stage tumors. Restoration of TSLC1 expression substantially suppressed tumor formation of PPC‐1 cells in nude mice. These findings indicate that alteration of TSLC1 is involved in prostate cancer.

Keywords: Prostate cancer, Tumor suppressor gene, TSLC1, Promoter methylation, Suppression of tumorigenicity

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REFERENCES

  • 1. ) Parker , S. L. , Tong , T. , Bolden , S. and Wingo , P. A.Cancer Statistics , 47 , 5 – 27 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Kakizoe , T.Figures on cancer in Japan—1997 . Foundation for Promotion of Cancer Research ( 1999. ). [Google Scholar]
  • 3. ) Ozen , M. and Pathak , S.Genetic alterations in human prostate cancer: a review of current literature . Anticancer Res. , 20 ( 3B ), 1905 – 1912 ( 2000. ). [PubMed] [Google Scholar]
  • 4. ) Murakami , Y. , Nobukuni , T. , Tamura , K. , Maruyama , T. , Sekiya , T. , Arai , Y. , Gomyou , H. , Tanigami , A. , Ohki , M. , Cabin , D. , Frischmeyer , P. , Hunt , P. and Reeves , R. H.Localization of tumor suppressor activity important in non‐small cell lung carcinoma on chromosome 11q . Proc. Natl. Acad. Sci. USA , 95 , 8153 – 8158 ( 1998. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Kuramochi , M. , Fukuhara , H. , Nobukuni , T. , Kanbe , T. , Maruyama , T. , Ghosh , H. P. , Pletcher , M. , Isomura , M. , Onizuka , M. , Kitamura , M. , Sekiya , T. , Reeves , R. H. and Murakami , Y.TSLC1 is a tumor suppressor gene in human non‐small cell lung cancer . Nat. Genet. , 27 , 427 – 430 ( 2001. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Gomyo , H. , Arai , Y. , Tanigami , A. , Murakami , Y. , Hattori , M. , Hosoda , F. , Arai , K. , Aikawa , Y. , Tsuda , H. , Hirohashi , S. , Asakawa , S. , Shimizu , N. , Soeda , E. , Sakaki , Y. and Ohki , M.A 2 Mb sequence‐ready contig map and a novel candidate tumor suppressor gene IGSF4 in the LOH region of chromosome 11q23.2 . Genomics , 62 , 139 – 146 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Brothman , A. R. , Lesho , L. J. , Somers , K. D. , Wright , G. L. , Jr. and Merchant , D. J.Phenotypic and cytogenetic characterization of a cell line derived from primary prostatic carcinoma . Int. J. Cancer , 44 , 898 – 903 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Frommer , M. , McDonald , L. E. , Millar , D. S. , Collis , C. M. , Watt , R , Grigg , G. W. , Molloy , P. L. and Paul , C. L.A genomic sequencing protocol that yields a positive display of 5‐methylcytosine residues in individual DNA strands . Proc. Natl. Acad. Sci. USA , 89 , 1827 – 1831 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Brothman , A. R. , Wilkins , P. C. , Sales , E. W. and Somers , K. D.Metastatic properties of the human prostatic cell line, PPC‐1, in athymic nude mice . J. Urol. , 145 , 1088 – 1091 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Partin , A. W. and Coffey , D. S.Benign and malignant prostatic neoplasms: human studies . Recent Prog. Harm. Res. , 49 , 293 – 331 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Morton , R. A. , Jr. , Ewing , C. M. , Watkins , J. J. and Isaacs , W. B.The E‐cadherin cell‐cell adhesion pathway in urologic malignancies . World J. Urol. , 13 , 364 – 368 ( 1994. ). [DOI] [PubMed] [Google Scholar]

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