caa a22 4500 397561954 CHVBK 20180308164818.0 cr unu---uuuuu 161202e19961204xx s 000 0 eng 10.1093/jnci/88.23.1731 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.23.1731 KiSS-1, a Novel Human Malignant Melanoma Metastasis-Suppressor Gene [Elektronische Daten] [Jeong-Hyung Lee, Mary E. Miele, Deana J. Hicks, Karen K. Phillips, Jeffery M. Trent, Bernard E. Weissman, Danny R. Welch] Background Microcell-mediated transfer of chromosome 6 into human C8161 and MelJuSo melanoma cells suppresses their ability to metastasize by at least 95% without affecting their tumorigenicity. This observation demonstrates that the ability to metastasize is a phenotype distinct from tumor formation and suggests that tumorigenic cells acquire meta-static capability only after accumulating additional genetic defects. These results also imply that mutations of genes on chromosome 6 are among those late genetic changes responsible for metastatic potential. They further suggest that a melanoma metastasis-suppressor gene(s) is encoded on chromosome 6 or is regulated by genes on chromosome 6. Purpose Our objective was to identify the gene(s) responsible for the suppression of metastasis in chromosome 6/melanoma cell hybrids Methods A modified subtractive hybridization technique was used to compare the expression of messenger RNAs (mRNAs), via an analysis of complementary DNAs (cDNAs), in metastatic cells (C8161 or MelJuSo) and nonmetastatic hybrid clones (neo6/C8161 or neo6/MelJuSo). Results A novel cDNA, designated KiSS-1, was isolated from malignant melanoma cells that had been suppressed for metastatic potential by the introduction of human chromosome 6. Northern blot analyses comparing mRNAs from a panel of human melanoma cells revealed that KiSS-1 mRNA expression occurred only in nonmetastatic melanoma cells. Expression of this mRNA in normal heart, brain, liver, lung, and skeletal muscle was undetect-able by northern blot analysis. Weak expression was found in the kidney and pancreas, but the highest expression was observed in the placenta. The KiSS-1 cDNA encodes a predominantly hydrophilic, 164 amino acid protein with a polyproline-rich domain indicative of an SH3 ligand (binds to the homology 3 domain of the oncoprotein Src) and a putative protein kinase C-α phosphorylation site. Transfection of a full-length KiSS-1 cDNA into C8161 melanoma cells suppressed metastasis in an expression-dependent manner Conclusions These data strongly suggest that KiSS-1 expression may suppress the metastatic potential of malignant melanoma cells. Implications KiSS-1 may be a useful marker for distinguishing metastatic melanomas from nonmetastatic melanomas. [J Natl Cancer Inst 1996;88: 1731-7] © Oxford University Press ARTICLES nationallicence Lee Jeong-Hyung Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut Miele Mary E. Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut Hicks Deana J. Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut Phillips Karen K. Department of Pathology, Lineberger Cancer Center, University of North Carolina Chapel Hill aut Trent Jeffery M. Division of Intramural Research, National Center for Human Genome Research Bethesda aut Weissman Bernard E. Department of Pathology, Lineberger Cancer Center, University of North Carolina Chapel Hill aut Welch Danny R. Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/23(1996-12-04), 1731-1737 0027-8874 88:23<1731 1996 88 jnci https://doi.org/10.1093/jnci/88.23.1731 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.23.1731 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lee Jeong-Hyung Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut NATIONALLICENCE 700 1- Miele Mary E. Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut NATIONALLICENCE 700 1- Hicks Deana J. Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut NATIONALLICENCE 700 1- Phillips Karen K. Department of Pathology, Lineberger Cancer Center, University of North Carolina Chapel Hill aut NATIONALLICENCE 700 1- Trent Jeffery M. Division of Intramural Research, National Center for Human Genome Research Bethesda aut NATIONALLICENCE 700 1- Weissman Bernard E. Department of Pathology, Lineberger Cancer Center, University of North Carolina Chapel Hill aut NATIONALLICENCE 700 1- Welch Danny R. Department of Experimental Pathology, The Jake Gittlen Cancer Research Institute, College of Medicine, The Pennsylvania State University Hershey aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/23(1996-12-04), 1731-1737 0027-8874 88:23<1731 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford