PACAP expression and distribution in human breast cancer and healthy tissue.

Pituitary adenylate cyclase-activating peptide (PACAP) is involved in various biological processes including cell growth, proliferation and differentiation. Here, we demonstrate for the first time the presence of both PACAP mRNA and PACAP immunoreactivity in human normal breast and breast carcinoma. Control, peritumoral and tumoral tissue pieces expressed preproPACAP mRNA since reverse transcription-polymerase chain reaction analysis gave an amplification product of the expected size (226 bp), which was further identified by analysis of the sequence. A main 19.9-kDa product (preproPACAP protein) was identified by Western blot in the three classes of breast tissue together with a small amount of a 14.6-kDa product (conceivably a result of partial processing by proprotein convertases). However, the mature peptide PACAP-38 was absent. The levels of both PACAP mRNA and PACAP immunoreactivity increased from normal to peritumoral and tumoral breast tissues but more patients must be considered to reinforce this feature. Immunohistochemistry showed the localization of PACAP immunoreactivity in alveolar epithelial cells in normal and carcinomatous tissues but also, at high density, in duct-like structures and in leucocytes in the connective tissue from breast cancer pieces. The results suggest that PACAP may play a role by autocrine/paracrine mechanisms in both normal human breast physiology and breast tumorigenesis.