Amplification, expression, and steroid regulation of the preprogalanin gene in human breast cancer.
The GALN gene encodes the preprogalanin protein that is cleaved to liberate 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 diverse tumor types including breast cancer. To determine whether GALN may contribute to the tumor phenotype resulting from 11q13 amplification, we examined GALN amplification and preprogalanin mRNA levels in breast tumors and cell lines. GALN was amplified in a subset of breast tumors and cell lines that carried 11q13 amplifications. Preprogalanin mRNA was expressed in the majority of breast cancer cell lines, but Northern analysis failed to demonstrate a relationship between GALN amplification and preprogalanin mRNA levels. Eight of eight estrogen receptor-positive cell lines expressed detectable preprogalanin mRNA, and further investigation showed that preprogalanin mRNA was increased by treatment with estradiol and progestin and decreased by the removal of serum or treatment with antiestrogens. Thus, GALN amplification is unlikely 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-positive cells, opening the wider question of the role of this steroid-regulated neuropeptide in the normal and cancerous breast.
Ormandy
C J
CJ
Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia. c.ormandy@garvan.unsw.edu.au
Lee
C S
CS
Ormandy
H F
HF
Fantl
V
V
Shine
J
J
Peters
G
G
Sutherland
R L
RL
D015152:Blotting, Northern; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002880:Chromosomes, Human, Pair 11; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D019004:Galanin / Q000096:biosynthesis* / Q000235:genetics*; D005784:Gene Amplification; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011372:Progestins / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004967:Estrogens; C056567:GAL protein, human; D011372:Progestins; D011498:Protein Precursors; D012333:RNA, Messenger; D013256:Steroids; D013196:Dihydrotestosterone; D003907:Dexamethasone; D019004:Galanin