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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18800

Title: Ectopic Notch1 Activation Alters Mammary Cell Fate During Puberty and Promotes the Development of Lactating Adenomas during Pregnancy
Authors: Kucharczuk, Aaron
Advisor: Egan, Sean
Department: Molecular and Medical Genetics
Keywords: Notch
Mammary Gland
Lactating Adenoma
ELF5+/ER- Cell Fate
Issue Date: 14-Feb-2010
Abstract: The role that each of the Notch receptors play in controlling alveolar development and cell fate determination in the mouse mammary gland has remained unclear. By utilizing a cre-conditional constitutively active intracellular Notch1 knock-in I define, in vivo, that ectopic Notch1 activation is sufficient to inhibit ductal outgrowth, cause the formation of alveolar-like cell accumulations, and promote Elf5+/ER- cell fate, at the expense of ER+ cell fate, in the mammary gland of pubescent mice. Furthermore, ectopic Notch1 in the pregnant mammary gland is sufficient to promote the formation of pregnancy/lactation-dependent lactating adenomas. These lactating adenomas consist of differentiated secretory cells and normally regress during involution but progress into non-regressing tumours after multiple pregnancies. These lactating adenomas exhibit decapitation secretions characteristic of apocrine differentiation. Together these results suggest that Notch1 may function to promote Elf5+/ER- cell fate and may be misregulated in pregnancy-associated masses and apocrine-carcinoma of the breast in humans.
URI: http://hdl.handle.net/1807/18800
Appears in Collections:Master
Department of Molecular Genetics - Master theses

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