Expression of epidermal growth factor in suprabasal cells of stratified squamous epithelia: implications for a role in differentiation.

There is a disparity in the fact that epidermal growth factor (EGF) can stimulate proliferation of a wide variety of cells in vitro, yet sites of synthesis for this polypeptide in vivo are generally associated with nonproliferative or differentiated cell populations. Unlike other known mitogenic members of the EGF family of ligands, EGF derives from a large (M(r) approximately 130,000) protein that contains multiple EGF-like domains; some of these domains contain putative Ca(2+)-binding sites. In the present study, the mouse vaginal epithelium was used as a prototype tissue to investigate expression of the EGF precursor by stratified squamous epithelia. Stratification and cornification in this tissue are estrogen dependent. In the fully differentiated epithelium, EGF precursor transcripts were detected by in situ hybridization in suprabasal cells; labeling was not observed in the proliferative basal cell compartment. Amplified transcripts of predicted size were detected in the vaginal organ by the reverse transcription-polymerase chain reaction and Northern hybridization of polyadenylated RNA. Antisera to mature EGF or to the COOH-terminal (cytoplasmic) domain of the precursor localized reactivity exclusively to cells of the granular layer. The staining with the precursor antiserum was localized along cell borders, which supports that this protein is translocated to the cell membrane following synthesis, a known property for precursors of EGF-like ligands. EGF expression was not apparent in the atrophic vaginal epithelium of castrates, which did not present a granular layer. Other stratified squamous epithelia in organs such as skin, esophagus, and tongue also revealed EGF/EGF precursor immunoreactivity in the granular layer.(ABSTRACT TRUNCATED AT 250 WORDS)