Methods: A human oral keratinocyte cell line T103C was transduced by recombinant retrovirus overexpressing HOXA7. Stable clones were generated following puromycin selection. These cells were used to determine the influence of HOXA7 on cell migration, cell proliferation and differentiation. Real time absolute quantitative PCR was used to determine the levels of differentiation markers following treatment with phorbol ester or by inducing differentiation at high cell density.
Results: Overexpression of HOXA7 led to increased keratinocyte migration and proliferation compared to control cells. Interestingly the rate of proliferation was dependent on cell density, single cells did not proliferate quickly while cells in groups proliferated very quickly. HOXA7 also suppressed differentiation by reducing expression of several differentiation markers when keratinocytes were induced to differentiate either by high density or by TPA treatment.
Conclusions: This study suggests that HOXA7 overexpression, as observed in oral cancer, induces cell migration, proliferation and suppresses differentiation. These characteristics are known hallmarks of keratinocytes undergoing oncogenesis. Based on these observations we predict an oncogenic role for HOXA7 in oral cancer.