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. 2001 Feb;92(2):140–151. doi: 10.1111/j.1349-7006.2001.tb01076.x

Structure, Expression and Chromosome Mapping of MLZE, a Novel Gene Which Is Preferentially Expressed in Metastatic Melanoma Cells

Kenji Watabe 1, Akihiko Ito 2, Hideo Asada 3, Yuichi Endo 5, Toshiko Kobayashi 6, Ken'i Nakamoto 1, Satoshi Itami 3, Sonshin Takao 7, Yasuhisa Shinomura 4, Takashi Aikou 7, Kunihiko Yoshikawa 3, Yuji Matsuzawa 4, Yukihiko Kitamura 2, Hiroshi Nojima 1,✉
PMCID: PMC5926699  PMID: 11223543

Abstract

We isolated a novel gene, termed MLZE, from a B16‐BL6 cDNA library after subtraction of B16‐F10 mRNA. Expression levels of mouse MLZE (mMLZE) increased in accordance with metastatic ability of B16 melanoma sublines. Human homolog of mMlze (hMlze) contained one leucine zipper structure and two potential nuclear localizing signals. Northern blot analysis of multiple human tissues showed that hMLZE was expressed primarily in trachea and spleen. We mapped the hMLZE gene (by fluorescence in situ hybridization) to 8q24.1‐2, which contains the c‐myc gene and is often amplified in malignant melanoma. Immunohistochemistry revealed that the number of hMlze‐positive cases was significantly larger in Clark levels III, IV and V melanomas (6/11=55%) than in Clark levels I and II melanomas (2/15=13%). In two cases of hMlze‐positive melanomas, the strength of hMlze staining increased substantially in the deep component of the tumor. Considering that melanomas above Clark level II are more metastatic than those below Clark level III, these findings suggested that MLZE is one of the genes whose expression is upregulated during the course of acquisition of metastatic potential in melanoma cells.

Keywords: B16 melanoma, c‐myc Metastasis, Tumor progression, Subtraction

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Sequences reported herein have been submitted to the DDBJ/GenBank/EMBL database under the accession numbers AB042405 (hMLZE cDNA) and AB042406 (mMLZE cDNA).

References

  • 1.Koh , H. K.Cutaneous melanoma . N. Engl. J. Med. , 325 , 171 – 182 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 2.Barnhill , R. L. , Mihm , M. C. , Fitzpatrick , T. B. . and Sober , E. J.Neoplasms: malignant melanoma . In “ Dermatology in General Medicine ,” ed. Fitzpatrick T. B. , Eisen A. Z. , Wolff K. , Freedberg I. M. and Austen K. F. . pp . 1078 – 1116 ( 1993. ). McGraw‐Hill; , New York . [Google Scholar]
  • 3.Clark , W. H. , From , L. , Bernardino , E. . and Mihm , M. C.The histogenesis and biologic behavior of primary human malignant melanomas of the skin . Cancer Res. , 29 , 705 – 726 ( 1969. ). [PubMed] [Google Scholar]
  • 4.Li , L. , Price , J. E. , Fan , D. , Zhang , R. D. , Bucana , C. D. . and Fidler , I. J.Correlation of growth capacity of human tumor cells in hard agarose with their in vivo proliferative capacity at specific metastatic sites . J. Natl. Cancer Inst. , 81 , 1406 – 1412 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 5.Albino , A. P.Genes involved in melanoma susceptibility and progression . Curr. Opin. Oncol. , 7 , 162 – 169 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 6.Reed , A. J. . and Albino , P. A.Update of diagnostic and prognosis markers in cutaneous malignant melanoma . Dermatol. Clin. , 17 , 631 – 643 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 7.Breslow , A.Thickness, cross‐sectional areas and depth of invasion in the prognosis of cutaneous melanoma . Ann. Surg. , 172 , 902 – 908 ( 1970. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Clark , W. H. , Jr. , Elder , D. E. , Guerry , D.4th , Braitman L. E. , Trock , B. J. , Schultz , D. , Synnestvedt , M. . and Halpern , A. C.Model predicting survival in stage I melanoma based on tumor progression . J. Natl. Cancer Inst. , 24 , 1893 – 1904 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 9.Hart , I. R.The selection and characterization of an invasive variant of the B16 melanoma . Am. J. Pathol. , 97 , 587 – 600 ( 1979. ). [PMC free article] [PubMed] [Google Scholar]
  • 10.Poste , G. , Doll , J. , Hart , I. R. . and Fidler , I. J.B16 melanoma variants with enhanced tissue‐invasive properties . Cancer Res. , 40 , 1636 – 1644 ( 1980. ). [PubMed] [Google Scholar]
  • 11.Kobori , M. , Ikeda , Y. , Nara , H. , Kato , M. , Kumegawa , M. , Nojima , H. . and Kawashima , H.Large scale isolation of osteoclast‐specific genes by an improved method involving the preparation of a subtracted cDNA library . Genes Cells , 3 , 459 – 475 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 12.Ito , A. , Kataoka , R. T. , Watanabe , M. , Nishiyama , K. , Mazaki , Y. , Sabe , H. , Kitamura , Y. . and Nojima , H.A truncated isoform of the PP2A B56 subunit promoted cell motility through paxillin phosphorylation . EMBO J. , 19 , 562 – 571 ( 2000. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Ito , A. , Katoh , F. , Kataoka , T. R. , Okada , M. , Tsubota , N. , Asada , H. , Yoshikawa , K. , Maeda , S. , Kitamura , Y. , Yamasaki , H. . and Nojima , H.A role of heterologous gap junctions between melanoma and endothelial cells in metastasis . J. Clin. Invest. , 105 , 1189 – 1197 ( 2000. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Nakaji , T. , Kataoka , R. T. , Watabe , K. , Nishiyama , K. , Nojima , H. , Shimada , Y. , Sato , F. , Matsushima , H. , Endo , Y. , Kuroda , Y. , Kitamura , Y. , Ito , A. . and Maeda , S.A new member of the GTPase superfamily that is upregulated in highly metastatic cells . Cancer Lett. , 147 , 139 – 147 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 15.Kataoka , T. R. , Ito , A. , Asada , H. , Watabe , K. , Nishiyama , K. , Nakamoto , K. , Itami , S. , Yoshikawa , K. , Ito , M. , Nojima , H. . and Kitamura , Y.Annexin VII as a novel marker for invasive phenotype of malignant melanoma . Jpn. J. Cancer Res. , 91 , 75 – 83 ( 2000. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Bennett , C. D. , Cooper , J. P. . and Hart , R. I.A line of non‐tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumor promoter for growth . Int. J. Cancer , 39 , 414 – 418 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 17.Endo , Y. , Fujita , T. , Tamura , K. , Tsuruga , H. . and Nojima , H.Structure and chromosomal assignment of the human cyclin G gene . Genomics , 38 , 92 – 95 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 18.Fujii , T. , Tamura , K. , Copeland , G. N. , Gilbert , J. D. , Jenkins , A. N. , Yomogida , K. , Tanaka , H. , Nishimune , Y. , Nojima , H. . and Abiko , Y.Sperizin is a murine RING zinc‐finger protein specifically expressed in haploid germ cells . Genomics , 57 , 94 – 101 ( 1999. ). [DOI] [PubMed] [Google Scholar]
  • 19.Kozak , M.Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs . Nucleic Acids Res. , 12 , 857 – 872 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Dingwall , C. . and Laskey , R. A.Nuclear targeting sequences‐a consensus ? Trends Biochem. Sci. , 16 , 478 – 481 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 21.Lazaris , A. C. , Theodoropoulos , G. E. , Aroni , K. , Saetta , A. . and Davaris , P. S.Immunohistochemical expression of c‐myc oncogene, heat shock protein 70 and HLA‐DR molecules in malignant cutaneous melanoma . Virchows Arch. , 426 , 461 – 467 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 22.Bergman , R. , Lurie , M. , Kerner , H. , Kilim , S. . and Friedman‐Birnbaum , R.Mode of c‐myc protein expression in Spitz nevi, common melanocytic nevi and malignant melanomas . J. Cutan. Pathol. , 24 , 219 – 222 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 23.Bastian , C. B. , LeBoit , E. P. , Hamm , H. , Brocjer , B. E. . and Pinkel , D.Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization . Cancer Res. , 58 , 2170 – 2175 ( 1998. ). [PubMed] [Google Scholar]
  • 24.Sonoda , G. , Palazzp , J. , du Manoir , S. , Godwin , A. K. , Feder , M. , Yakushiji , M. . and Testa , J. R.Comparative genomic hybridization detects frequent overrepresentation of chromosomal material from 3q26, 8q24, and 20q13 in human ovarian carcinomas . Genes Chromosom. Cancer , 20 , 320 – 328 ( 1997. ). [PubMed] [Google Scholar]
  • 25.Nishizaki , T. , Ozaki , S. , Harada , K. , Ito , H. , Arai , H. , Beppu , T. . and Sasaki , K.Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization . Genes Chromosom. Cancer , 21 , 340 – 346 ( 1998. ). [DOI] [PubMed] [Google Scholar]
  • 26.Muleris , M. , Almedia , A. , Gerbault‐Seureau , M. , Malfoy , B. . and Dutrellaux , B.Detection of DNA amplification in 17 primary breast carcinomas with homogeneously staining regions by a modified comparative genomic hybridization technique . Genes Chromosom. Cancer , 10 , 160 – 170 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 27.Testa , J. R. , Liu , Z. , Feder , M. , Bell , D. W. , Balsara , B. , Cheng , J. Q. . and Taguchi , T.Advances in the analysis of chromosome alterations in human lung carcinomas . Cancer Genet. Cytogenet , 95 , 20 – 32 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 28.Bergh , J. C.Gene amplification in human lung cancer. The myc family genes and other proto‐oncogenes and growth factor genes . Am. Rev. Respir. Dis. , 142 , 20 – 26 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 29.Gown , A. M. , Vogel , A. M. , Hoak , D. , Gough , F. . and McNutt , M. A.Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes . Am. J. Pathol. , 123 , 195 – 203 ( 1986. ). [PMC free article] [PubMed] [Google Scholar]
  • 30.King , R. , Weilbaecher , K. N. , McGill , G. , Cooley , E. , Mihm , M. . and Fisher , D.E. Microphthalmia transcription factor. A sensitive and specific melanocyte marker for melanoma diagnosis . Am. J. Pathol. , 155 , 731 – 738 ( 1999. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

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