Expression of the alpha-fetoprotein gene in human breast cancer

Recently, evidence was obtained that the ability to take up alpha-fetoprotein (alpha-FP), which is characteristic of fetal cells, may be required both in vivo and in vitro by different types of human and animal tumor cells via expression of specific alpha-FP receptors. Mammary gland carcinomas belong to this class of tumor. In some neoplasms, expression of alpha-FP receptors is concomitant with activation of the alpha-FP gene and synthesis of the protein, suggesting that an autocrine alpha-FP/alpha-FP-receptor pathway is operational in these tumors. In the present work, 18 human breast cancer biopsy specimens were subjected 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 fibroblasts and lymphocytes infiltrating tumor nests and in adipocytes adjacent to tumor areas, while the malignant cells themselves were hardly labeled. This suggests paracrine stimulation of the alpha-FP gene, probably as a result of epithelial-mesenchymal interactions. Pathological implications arise from the ability of alpha-FP to regulate growth, either alone or synergistically with other growth factors, as well as its ability to enhance fatty acid entry into proliferating cells.