KiSS-1, a novel human malignant melanoma metastasis-suppressor gene
JH Lee, ME Miele, DJ Hicks, KK Phillips… - JNCI: Journal of the …, 1996 - academic.oup.com
JH Lee, ME Miele, DJ Hicks, KK Phillips, JM Trent, BE Weissman, DR Welch
JNCI: Journal of the National Cancer Institute, 1996•academic.oup.comBackground 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 …
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 …
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