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Amplification, Expression, and Steroid Regulation of the Preprogalanin Gene in Human Breast Cancer¹

Cancer Resarch [C. J. O., C. S. L. L., R. L. S.] and Neurobiology Programs [H. F. O., J. S.], Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia, and Molecular Oncology Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom [V. F., G. P.]

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.

¹ Supported by the National Health and Medical Research Council of Australia, the New South Wales State Cancer Council, and the Kathleen Cunningham Foundation, Australia. C. J. O. was a C. J. Martin Fellow of the National Health and Medical Research Council of Australia, and H. F. O. held a postgraduate scholarship from the National Health and Medical Research Council of Australia.

² To whom requests for reprints should be addressed, at Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst Sydney, New South Wales 2010, Australia. E-mail: c.ormandy@garvan.unsw.edu.au.

Received 12/22/97. Accepted 2/17/98.

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