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

• Published in: Cancer science Vol. 92; no. 2; pp. 140 - 151
• Main Authors: Watabe, Kenji, Ito, Akihiko, Asada, Hideo, Endo, Yuichi, Kobayashi, Toshiko, Nakamoto, Ken'i, Itami, Satoshi, Takao, Sonshin, Shinomura, Yasuhisa, Aikou, Takashi, Yoshikawa, Kunihiko, Matsuzawa, Yuji, Kitamura, Yukihiko, Nojima, Hiroshi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2001; Japanese Cancer Association; John Wiley & Sons, Inc
• Subjects: Adult; Aged; Amino Acid Sequence; Animals; B16 melanoma; Base Sequence; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Chromosome Mapping; Chromosomes, Human, Pair 8; Cloning, Molecular; c‐myc Metastasis; Dermatology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Female; Fluorescence in situ hybridization; Gene expression; Gene Expression Regulation, Neoplastic; Gene mapping; Humans; Immunohistochemistry; Leucine zipper proteins; Male; Medical sciences; Melanoma; Melanoma - diagnosis; Melanoma - genetics; Melanoma - metabolism; Metastases; Metastasis; Mice; Middle Aged; Molecular Sequence Data; mRNA; Myc protein; Neoplasm Metastasis; Nuclear Localization Signals; Proto-Oncogene Proteins c-myc - metabolism; RNA, Messenger - biosynthesis; Skin cancer; Skin Neoplasms - diagnosis; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Spleen; Subtraction; Tissue Distribution; Trachea; Tumor Cells, Cultured; Tumor progression; Tumors of the skin and soft tissue. Premalignant lesions; Up-Regulation; Human; Skin disease; Melanoma; Chromosome; Primary structure; Malignant tumor; Metastasis; Gene expression; Carcinogenesis; Gene; Tumor progression; Cytogenetics; Genetics; Skin; Localization
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.2001.tb01076.x

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.