We have demonstrated progressive enhancement of expression of homeobox genes on the HOX A cluster (found on chromosome 7) during retinoic acid induced differentiation of PA-1 human ovarian teratocarcinoma cells. Transformation by an N-ras oncogene inhibi ts this process. We hypothesize that homeobox genes regulate the cascades of changes in gene expression responsible for growth arrest and differentiation. We have shown that constitutive expression of Hox A4 (1.4) in the absence of RA can induce a diffe rentiated morphology to PA-1 cells and can restore RA responsiveness to differentiation resistant N-ras transformed PA-1 cells. To understand the mechanism by which this occurs, we need to know whether this property is unique to Hox A4 or will other homeobox genes also restore RA induced differentiation.