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We previously reported that overexpression of the HOXD3 homeobox gene in human erythroleukemia HEL cells gave rise to changes in cell adhesiveness. In the present study, we examined the consequences of over- or underexpression of HOXD3 in HEL cells for colony morphology, the ability to adhere to fibronectin, and expression of cell adhesion molecules in order to further confirm the effects attributed to varied levels of HOXD3 expression. Cells overexpressing HOXD3, which formed compact colonies composed of condensed cells, had a greater affinity for fibronectin and expressed higher levels of β3 integrin mRNA than the control cells transfected with an empty vector. Cells which did not express any HOXD3 mRNA failed to form colonies, had a low affinity for fibronectin, and expressed low levels of β3 integrin mRNA. Instead, the cells underexpressing HOXD3 exhibited higher levels of cadherin 4 mRNA than the control and cells overexpressing HOXD3. These results demonstrate that the ability to form colonies and attach to fibronectin in HEL cells was dependent on levels of HOXD3 expression, and that HOXD3 served as a switch from cadherin 4 to β3 integrin gene expression.

HOXD3 Mediates the Switchover of Cadherin 4 to β3 Integrin Gene Expression in Human Erythroleukemia HEL Cells