The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells.
The Oct transcription factors N-Oct-3 and N-Oct-5 are differentially expressed in normal melanocytes, melanoma tumors and cell lines. We have cloned the human brn-2 gene and have shown that it encodes both the N-Oct-3 and N-Oct-5 octamer binding activities detected in melanoma cells. The brn-2 genomic locus has been mapped to chromosome 6q16 and although chromosomal aberrations are common in this region in melanoma, no deletion or rearrangement of the brn-2 gene in melanoma cell lines was observed. Sequencing of the entire gene showed that there are no intervening sequences within the open reading frame. Antisense RNA-mediated inhibition of brn-2 gene expression in melanoma cells was associated with a change in morphology and loss of melanocytic and neural crest markers, including the melanocyte transcription factor microphthalmia and the TYRP pigmentation genes. In addition, loss of brn-2 in these cells resulted in the complete loss of ability to form tumors in SCID and nu/nu mice. These results suggest roles for brn-2 in the determination of the melanocytic lineage and in the tumorigenic phenotype of melanoma.
Thomson
J A
JA
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Herston, Australia.
Murphy
K
K
Baker
E
E
Sutherland
G R
GR
Parsons
P G
PG
Sturm
R A
RA
Thomson
F
F
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002454:Cell Differentiation; D002460:Cell Line; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6; D004273:DNA, Neoplasm / Q000032:analysis; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D050809:POU Domain Factors; D016372:RNA, Antisense / Q000494:pharmacology; D015183:Restriction Mapping; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; D050809:POU Domain Factors; D016372:RNA, Antisense; D014157:Transcription Factors; C085076:transcription factor Brn-2; D018799:Intercellular Adhesion Molecule-1