Homeobox genes encode sequence-specific
DNA-binding proteins that are involved in the regulation of gene expression during embryonic development. In this study, we examined the expression of
homeobox proteins in human
cancer. Antiserum was obtained against a synthetic
peptide derived from the highly conserved 60
amino acid homeodomain. This
peptide antiserum recognized a
protein species of molecular weight 63,000 in immunoblots of nuclear extracts obtained from several tumor cell lines. The predominant molecular weight 63,000
nuclear protein recognized by the
peptide antiserum was then isolated and used to elicit a rabbit antiserum. In immunostaining, both
antisera reacted with the nuclei of cultured tumor cells. In tissue sections of human
carcinoma, nuclear immunoreactivity was observed in the
tumor cells in 40 of 42 cases examined. Adjacent normal epithelial tissue obtained from the same patients exhibited little immunoreactivity. Both the
peptide antiserum and the polyclonal antiserum against the native
protein immunoblotted a molecular weight 63,000
protein in nuclear extracts of
tumor tissue, but not significantly in extracts of normal tissue. At the molecular level, the presence of the homeobox transcript in human
carcinoma was documented by in situ hybridization and
RNase protection mapping. These results demonstrate that human
cancer is associated with the expression of
homeobox proteins. Such
homeobox proteins, as well as other regulatory
proteins, could be involved in the initiation or maintenance of the malignant phenotype.