AMPLIFICATION, EXPRESSION, AND STEROID REGULATION OF THE PREPROGALANIN GENE IN HUMAN BREAST-CANCER

The GALN gene encodes the preprogalanin protein that is cleaved to lib erate the galanin peptide, a neuropeptide and tumor cell mitogen, and the galanin message-associated peptide, which is of unknown function, GALN is located at chromosome 11q13, a frequently amplified locus in d iverse tumor types including breast cancer, To determine whether GALN may contribute to the tumor phenotype resulting from 11q13 amplificati on, we examined GALN amplification and preprogalanin mRNA levels in br east tumors and cell lines, GALN was amplified in a subset of breast t umors and cell lines that carried 11q13 amplifications, Preprogalanin mRNA was expressed in the majority of breast cancer cell lines, but No rthern analysis failed to demonstrate a relationship between GALN ampl ification and preprogalanin mRNA levels, Eight of eight estrogen recep tor-positive cell lines expressed detectable preprogalanin mRNA, and f urther investigation showed that preprogalanin mRNA was increased by t reatment with estradiol and progestin and decreased by the removal of serum or treatment with antiestrogens, Thus, GALN amplification is unl ikely to contribute to the phenotype conferred by 11q13 amplification in breast cancer, but preprogalanin mRNA is expressed by breast cancer cells and is under steroid hormone control in estrogen receptor-posit ive cells, opening the wider question of the role of this steroid-regu lated neuropeptide in the normal and cancerous breast.