Mammary Apoptosis

Quarrie, Lynda H (1996) Mammary Apoptosis. PhD thesis, University of Glasgow.

Abstract

This thesis examines the importance of mammary apoptosis during lactation and involution and investigates some of the factors which influence apoptotic rates in the mammary gland. The extent of apoptosis in mammary tissue was assessed using (32P)dCTP nick-end labelled DNA to visualise DNA laddering. Changes in DNA laddering were compared with histological techniques to determine general tissue morphology, chromatin changes and presence of apoptotic bodies and localisation of dying cells (ISEL). Where possible these measurements were combined with gene expression studies to determine changes in expression of proteases, inhibitors of proteases, p53 and bax. As shown previously, apoptosis is important for cell removal in rodents during natural weaning and after litter removal at peak lactation. In both situations apoptosis followed a similar time course, however, after litter removal in declining lactation the increase in apoptosis was more rapid. Apoptosis also appeared to be essential between lactation cycles even when the interval between lactation cycles was reduced to a minimum by mating at post partum oestrus. DNA laddering was detected at peak lactation of mice, rats and goats, suggesting that cell turnover is a physiological process in lactating tissue. This study also investigated the regulation of mammary apoptosis. The effects of hormonal status of lactating rats and milk stasis in mice and goats were investigated. Prolactin, acting as a cell survival factor, was shown to influence apoptosis. Growth hormone action was more subtle, and was achieved through a different mechanism to that of prolactin. A local mechanism for regulating mammary apoptosis was demonstrated in mice where unilateral milk stasis induced apoptosis at levels similar to litter removal. Apoptosis was also induced in goats by a local control mechanism since unilateral cessation of milking increased apoptosis to a greater degree in unmilked glands compared to milked glands. Finally, possible mechanisms of local and systemic control were studied during lumen formation when mammary cells were cultured on extracellular matrix, in vitro. After several days on extracellular matrix solid clumps of epithelial cells form hollow spherical structures. Cells on the periphery of the cell clump survive, and only these have access to laminin, (a component of the extracellular matrix). Cells in the centre of the clumps die by apoptosis, and this produces luminal spaces within the structures. An IGFBP is also elevated at the time of apoptotic cell removal, and may be involved in blocking IGF-1 activity in cells that are to die. In conclusion, this study demonstrates the widespread importance of apoptosis in the mammary gland, the local and systemic regulation of the process and some clues as to the mechanism of apoptosis in mammary cells.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Colin Wilde
• Keywords: Cellular biology
• Date of Award: 1996
• Depositing User: Enlighten Team
• Unique ID: glathesis:1996-75592
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 19:21
• Last Modified: 19 Nov 2019 19:21
• URI: https://theses.gla.ac.uk/id/eprint/75592