Investigation of the Role of the Mitogenic Neuropeptide Galanin in Mammary Gland Development and Carcinogenesis
Abstract
Mammary gland development in the galanin knockout mouse has been the focus of activity during the previous year. The galanin knockout was found to show failure of mammary development during the first pregnancy which resulted in a 100% failure of lactation. Subsequent pregnancies resulted in normal development and successful lactation. Mammary gland recombination/transplantation showed that this effect was not mammary epithelial cell autonomous, and did not require stromal galanin, ruling out an autocrine role for galanin. Analysis of the galanin receptor 1 knockout revealed no lactational deficit, ruling out an autocrine role for galanin via this receptor. An endocrine role via the other receptors is currently under investigation using whole mammary gland organ culture Similarity to the prolactin knockout phenotype suggested prolactin as a mediator of an indirect effect of galanin, and attempts to rescue developmental failure with osmotic minipump administration of prolactin were successful. The expression pattern of galanin and its receptors is under investigation at various stages of mouse mammary development. Studies in human material have used cell lines to date, where the expression patterns of galanin and its receptors have been determined, allowing the selection of suitable cell lines for in vitro analysis of the potential growth promoting action of galanin. Experiments using 96 well plate MTT proliferation assays have proved difficult due to variability of response, and ongoing work has shifted to the use of clonogenic assays. The formation of arrayed human breast cancer biopsies has begun to allow the analysis of galanin expression during disease progression. The mouse work is currently being prepared for publication. During these experiments observations were made regarding the role of the mouse stroma in the control of mammary ductal branching patterns and a brief communication has been prepared and submitted for publication.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA385952
Entities
People
- Christopher Ormandy
Organizations
- Garvan Institute of Medical Research