EXPRESSION OF THE ALPHA-FETOPROTEIN GENE IN HUMAN BREAST-CANCER

Recently, evidence was obtained that the ability to take up alpha-feto protein (alpha-FP), which is characteristic of fetal cells, may be req uired both in vivo and in vitro by different types of human and animal tumor cells via expression of specific alpha-FP receptors. Mammary gl and carcinomas belong to this class of tumor. In some neoplasms, expre ssion of alpha-FP receptors is concomitant with activation of the alph a-FP gene and synthesis of the protein, suggesting that an autocrine a lpha-FP/alpha-FP-receptor pathway is operational in these tumors. In t he present work, 18 human breast cancer biopsy specimens were subjecte d to in situ hybridization with a human alpha-FP cDNA probe. Positive labeling for alpha-FP mRNA transcripts was seen in 8 of the specimens. Surprisingly, strong positive signals were seen in stromal fibroblast s and lymphocytes infiltrating tumor nests and in adipocytes adjacent to tumor areas, while the malignant cells themselves were hardly label ed. This suggests paracrine stimulation of the alpha-FP gene, probably as a result of epithelial-mesenchymal interactions. Pathological impl ications arise from the ability of alpha-FP to regulate growth, either alone or synergistically with other growth factors, as well as its ab ility to enhance fatty acid entry into proliferating cells.