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Investigating the Role of the Mutant Estrogen Receptor in Mammary Gland Development and Tumorigenesis.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Investigating the Role of the Mutant Estrogen Receptor in Mammary Gland Development and Tumorigenesis./
Author:	Moore, Michaela Jane.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	74 p.
Notes:	Source: Masters Abstracts International, Volume: 82-10.
Contained By:	Masters Abstracts International82-10.
Subject:	Tumorigenesis. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28384052
ISBN:	9798708710468

Investigating the Role of the Mutant Estrogen Receptor in Mammary Gland Development and Tumorigenesis.
Moore, Michaela Jane.

Investigating the Role of the Mutant Estrogen Receptor in Mammary Gland Development and Tumorigenesis. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 74 p.

Source: Masters Abstracts International, Volume: 82-10.

Thesis (M.Sc.)--McGill University (Canada), 2020.

This item must not be sold to any third party vendors.

Hormone receptor-positive breast cancer accounts for over 70% of breast cancer diagnoses worldwide. When diagnosed early, the prognosis for patients with estrogen receptor-positive breast cancer is very good and there are several treatment options that have been developed over the last fifty years. However, this disease presents us with a challenge: resistance to endocrine therapy occurs in roughly 25% of cases and recurrence of the tumour or of secondary tumours is common. Mutations in the estrogen receptor are found in endocrine resistant metastatic breast cancer, but rarely in primary tumours. The mechanisms underlying endocrine resistance have not been fully explored and are still overall poorly understood. Because of this, we generated the first immunocompetent mouse model that expresses one of the most common mutations that occurs in human metastatic ER+ breast cancer: ESR1Y537S (ESR1Y541S in mice). We have shown that a fullbody knock-in of this point-activated mutant results in a dramatic phenotype, but mammary epithelium-specific expression does not seem to affect the development of the ductal tree in virgin mice or during reproductive development. Ovariectomy of these mice prior to puberty inhibits the development of the mammary gland, however, in the full-body context, a ductal tree appears in 100% of cases. Expression of ESR1Y541S in a PI3K-driven model of breast cancer also does not affect onset or tumour growth overall but may affect metastasis and signalling in later stages or in secondary tumours. This remains to be investigated.

ISBN: 9798708710468Subjects--Topical Terms:

3561727
Tumorigenesis.
Subjects--Index Terms:

Mutant estrogen receptor

Investigating the Role of the Mutant Estrogen Receptor in Mammary Gland Development and Tumorigenesis.
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245 1 0 $a Investigating the Role of the Mutant Estrogen Receptor in Mammary Gland Development and Tumorigenesis.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 74 p.
500 $a Source: Masters Abstracts International, Volume: 82-10.
500 $a Advisor: Muller, William Joseph.
502 $a Thesis (M.Sc.)--McGill University (Canada), 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Hormone receptor-positive breast cancer accounts for over 70% of breast cancer diagnoses worldwide. When diagnosed early, the prognosis for patients with estrogen receptor-positive breast cancer is very good and there are several treatment options that have been developed over the last fifty years. However, this disease presents us with a challenge: resistance to endocrine therapy occurs in roughly 25% of cases and recurrence of the tumour or of secondary tumours is common. Mutations in the estrogen receptor are found in endocrine resistant metastatic breast cancer, but rarely in primary tumours. The mechanisms underlying endocrine resistance have not been fully explored and are still overall poorly understood. Because of this, we generated the first immunocompetent mouse model that expresses one of the most common mutations that occurs in human metastatic ER+ breast cancer: ESR1Y537S (ESR1Y541S in mice). We have shown that a fullbody knock-in of this point-activated mutant results in a dramatic phenotype, but mammary epithelium-specific expression does not seem to affect the development of the ductal tree in virgin mice or during reproductive development. Ovariectomy of these mice prior to puberty inhibits the development of the mammary gland, however, in the full-body context, a ductal tree appears in 100% of cases. Expression of ESR1Y541S in a PI3K-driven model of breast cancer also does not affect onset or tumour growth overall but may affect metastasis and signalling in later stages or in secondary tumours. This remains to be investigated.
520 $a Les cancers du sein a recepteurs hormonaux positifs representent 70% des cancers du sein a travers le monde. Un diagnostique precoce pour un cancer du sein positif aux recepteurs d'oestrogenes permet generalement un pronostique favorable puisque plusieurs options de traitements ont etes developpees depuis les 50 dernieres annees. Par contre, cette maladie represente encore un defi pour la recherche puisqu'une resistance a l'hormonotherapie se developpe dans 25% des cas et la recurrence de la tumeur au site originel ou secondaire est frequente. Plusieurs mutations dans le recepteur oestrogen ont ete identifiees dans les sites de metastase des femmes atteintes d'un cancer du sein resistant a l'hormonotherapie, mais tres rarement dans les tumeurs primaires. Les mecanismes sous-jacents cette resistance n'ont pas ete pleinement explores et demeurent toujours peu compris. Pour cette raison, nous avons genere le premier modele de souris immunocompetente qui exprime une des mutations les plus communes qui se retrouve dans les metastases des cancers du sein ER+ : ESR1Y537S (ESR1Y541S chez la souris). Nous avons montre que l'expression de cette mutation dans le genome entier d'une souris provoque un phenotype severe, mais que l'expression specifique de cette meme mutation dans les cellules epitheliales mammaires des souris n'affecte pas le developpement des canaux mammaires des femelles vierges ni meme durant le developpement reproducteur. L'overactomie de ces souris avant la puberte inbibe le developpement des glandes mammaires, neamoins, dans le contexte de l'expression dans le genome entier, le developpement des glandes mammaires se produit dans 100% des cas. L'expression dans les glandes mammaires de la mutation ESR1Y541S dans un model de cancer de souris exprimant l'antigene T moyen du polyomavirus n'affecte pas non plus le temps de formation des tumeurs ni la croissance de celles-ci, mais pourrait affecter les metastases et les voies de signalisation a un stage plus avance ou dans les tumeurs secondaires. Ces elements restent a explorer.
590 $a School code: 0781.
650 4 $a Tumorigenesis. $3 3561727
650 4 $a Oophorectomy. $3 3686277
650 4 $a Metastasis. $3 818532
650 4 $a Tumors. $3 893964
650 4 $a Estrogens. $3 3563093
650 4 $a Kinases. $3 3558077
650 4 $a Mutation. $3 837917
650 4 $a Breast cancer. $3 3543523
650 4 $a Medical research. $2 bicssc $3 1556686
653 $a Mutant estrogen receptor
653 $a Mammary gland development
653 $a Tumorigenesis
690 $a 0992
690 $a 0487
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710 2 $a McGill University (Canada). $3 1018122
773 0 $t Masters Abstracts International $g 82-10.
790 $a 0781
791 $a M.Sc.
792 $a 2020
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28384052