Abstract
The TSLL2/IGSF4C encodes an immunoglobulin (Ig) superfamily molecule showing significant homology with a lung tumor suppressor, TSLC1. The TSLL2 protein of 55 kDa is mainly expressed in the kidney, bladder, and prostate in addition to the brain. Here, we report the biological significance of TSLL2 in the urinary tissues. An immunohistochemical study reveals that TSLL2 is expressed at the cell–cell attachment sites in the renal tubules, the transitional epithelia of the bladder, and the glandular epithelia of the prostate. Confocal microscopy analysis demonstrates that TSLL2 is localized in the lateral membranes in polarized Mardin-Darby canine kidney (MDCK) cells. TSLL2 forms homo-dimers and its overexpression induces aggregation of suspended MDCK cells in a Ca2+/Mg2+-independent manner, suggesting that it is involved in cell adhesion through homophilic trans-interaction. The TSLL2 gene is mapped on the chromosomal region 19q13.2, whose loss of heterozygosity has been frequently reported in prostate cancer. TSLL2 protein is lost in nine of nine primary prostate cancers and in a prostate cancer cell, PPC-1. Introduction of TSLL2 into PPC-1 strongly suppresses subcutaneous tumor formation in nude mice. These results suggest that TSLL2 is a new member of the Ig superfamily cell adhesion molecules and is a tumor-suppressor candidate in prostate cancer.
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References
Astbury C, Jackson-Cook CK, Culp SH, Paisley TE, Ware JL . (2001). Genes Chromosomes Cancer 31: 143–155.
Benson DL, Schnapp LM, Shapiro L, Huntley GW . (2000). Trends Cell Biol 10: 473–482.
Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET et al. (2002). Science 297: 1525–1531.
Brothman AR, Wilkins PC, Sales EW, Somers KD . (1991). J Urol 145: 1088–1091.
Fujita E, Soyama A, Momoi T . (2003). Exp Cell Res 287: 57–66.
Fukami T, Fukuhara H, Kuramochi M, Maruyama T, Isogai K, Sakamoto M et al. (2003a). Int J Cancer 107: 53–59.
Fukami T, Satoh H, Williams YN, Masuda M, Fukuhara H, Maruyama T et al. (2003b). Gene 323: 11–18.
Fukuhara H, Kuramochi M, Fukami T, Kasahara K, Furuhata M, Nobukuni T et al. (2002). Jpn J Cancer Res 93: 605–609.
Fukuhara H, Kuramochi M, Nobukuni T, Fukami T, Saino M, Maruyama T et al. (2001). Oncogene 20: 5401–5407.
Gao AC, Lou W, Ichikawa T, Denmeade SR, Barrett JC, Isaacs JT . (1999). Prostate 38: 46–54.
Gomyo H, Arai Y, Tanigami A, Murakami Y, Hattori M, Hosoda F et al. (1999). Genomics 62: 139–146.
Hynes RO . (1999). Trends Cell Biol 9: M33–7.
Ito T, Shimada Y, Hashimoto Y, Kaganoi J, Kan T, Watanabe G et al. (2003). Cancer Res 63: 6320–6326.
Kuramochi M, Fukuhara H, Nobukuni T, Kanbe T, Maruyama T, Ghosh HP et al. (2001). Nat Genet 27: 427–430.
Masuda M, Yageta M, Fukuhara H, Kuramochi M, Maruyama T, Nomoto A et al. (2002). J Biol Chem 277: 31014–31019.
Murakami Y . (2002). Oncogene 21: 6936–6948.
Murakami Y . (2005). Cancer Sci 96: 543–552.
Neville PJ, Conti DV, Krumroy LM, Catalona WJ, Suarez BK, Witte JS et al. (2003). Genes Chromosomes Cancer 36: 332–339.
Ozen M, Pathak S . (2000). Anticancer Res 20 (3B): 1905–1912.
Parker SL, Tong T, Bolden S, Wingo PA . (1997). Cancer Statist 47: 5–27.
Satoh-Horikawa K, Nakanishi H, Takahashi K, Miyahara M, Nishimura M, Tachibana K et al. (2000). J Biol Chem 275: 10291–10299.
Shingai T, Ikeda W, Kakunaga S, Morimoto K, Takekuni K, Itoh S et al. (2003). J Biol Chem 278: 35421–35427.
Slager SL, Schaid DJ, Cunningham JM, McDonnell SK, Marks AF, Peterson BJ et al. (2003). Am J Hum Genet 72: 759–762.
Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA . (1986). J Cell Biol 103: 755–766.
Takai Y, Irie K, Shimizu K, Sakisaka T, Ikeda W . (2003). Cancer Sci 94: 655–667.
Wakayama T, Ohashi K, Mizuno K, Iseki S . (2001). Mol Reprod Dev 60: 158–164.
Yoshida C, Takeichi M . (1982). Cell 28: 217–224.
Acknowledgements
We thank Dr Tesshi Yamada at NCC for his generous help with the Bio-Rad Radiance 2000 confocal scanning system and Drs Yoshiyuki Ishii and Satoshi Sekiguchi at the University of Tokyo for their generous support of our pathological studies. This work was supported in part by a Grant-in-Aid for the Third-Term Comprehensive Control Research for Cancer from the Ministry of Health, Labor, and Welfare of Japan; a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; and a Grant from the Program for the Promotion of Fundamental Studies in Health Sciences of Pharmaceutical and Medical Devices Agency (PMDA) of Japan; MM is a recipient of a Research Fellowship from PMDA. MS-Y is a recipient of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research (Japan).
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Williams, Y., Masuda, M., Sakurai-Yageta, M. et al. Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4. Oncogene 25, 1446–1453 (2006). https://doi.org/10.1038/sj.onc.1209192
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DOI: https://doi.org/10.1038/sj.onc.1209192
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