PMID- 8944003
OWN - NLM
STAT- MEDLINE
DCOM- 19961223
LR  - 20220318
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 88
IP  - 23
DP  - 1996 Dec 4
TI  - KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.
PG  - 1731-7
AB  - BACKGROUND: Microcell-mediated transfer of chromosome 6 into human C8161 and 
      MelJuSo melanoma cell 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 metastatic 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 undetectable 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-alpha 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.
FAU - Lee, J H
AU  - Lee JH
AD  - Department of Experimental Pathology, Jake Gittlen Cancer Research Institute, 
      College of Medicine, Pennsylvania State University, Hershey 17033-0850, USA.
FAU - Miele, M E
AU  - Miele ME
FAU - Hicks, D J
AU  - Hicks DJ
FAU - Phillips, K K
AU  - Phillips KK
FAU - Trent, J M
AU  - Trent JM
FAU - Weissman, B E
AU  - Weissman BE
FAU - Welch, D R
AU  - Welch DR
LA  - eng
SI  - GENBANK/U43527
GR  - CA44470/CA/NCI NIH HHS/United States
GR  - CA62168/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
SB  - IM
EIN - J Natl Cancer Inst 1997 Oct 15;89(20):1549
CIN - J Natl Cancer Inst. 1996 Dec 4;88(23):1700-3. PMID: 8943996
MH  - Amino Acid Sequence
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Northern
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Melanoma/*genetics/secondary
MH  - Mice
MH  - Mice, Nude
MH  - Molecular Sequence Data
MH  - Neoplasm Metastasis/*genetics
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1996/12/04 00:00
MHDA- 1996/12/04 00:01
CRDT- 1996/12/04 00:00
PHST- 1996/12/04 00:00 [pubmed]
PHST- 1996/12/04 00:01 [medline]
PHST- 1996/12/04 00:00 [entrez]
AID - 10.1093/jnci/88.23.1731 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1996 Dec 4;88(23):1731-7. doi: 10.1093/jnci/88.23.1731.