Identification and temporal expression pattern of genes modulated during irreversible growth arrest and terminal differentiation in human melanoma cells

Abnormalities in differentiation are common occurrences in human cancers, T reatment-of human melanoma cells with the combination of recombinant human fibroblast interferon (IFN-beta) and the antileukemic compound mezerein (ME Z) results in a loss of tumorigenic potential that correlates with an irrev ersible suppression in proliferative ability and induction of terminal diff erentiation. It is hypothesized that this is associated with the differenti al expression of genes that may directly regulate cancer cell growth and di fferentiation. To define the relevant gene expression changes that correlat e with and potentially control these important cellular processes a differe ntiation induction subtraction hybridization (DISH) scheme is being used,A temporally spaced subtracted differentiation inducer treated (TSS) cDNA lib rary was constructed and differentially expressed DISH clones were isolated and evaluated using a high throughput microchip cDNA (Synteni) array scree ning approach, Verification of differential, gene expression for specific c DNAs was confirmed by Northern blotting. The temporal kinetics of regulatio n and the expression pattern of DISH genes were also evaluated by microchip cDNA array screening. Using this approach with 1000 DISH cDNA clones (simi lar to 10% of the DISH library) has resulted in the identification and clon ing of both 26 known and 11 novel cDNAs of potential relevance to growth co ntrol and terminal differentiation in human melanoma cells.