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Title: GPR30 and ERα36 and their potential role in breast and endometrial cancers
Author: Doran, Heather
ISNI:       0000 0004 2739 8899
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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It is currently poorly understood how hormones like oestrogen can elicit a rapid non-genomic response from cells via their traditional nuclear receptors. It has been known for some time that some cells, although lacking the canonical oestrogen receptors (ERs), still display rapid non-genomic signalling in response to oestrogen. Recently, a G protein coupled receptor; GPR30 (or GPER) and an alternative splice variant of the traditional ERα (ERα36) have been proposed as alternative oestrogen receptors that may mediate these non-genomic effects. This study investigated the presence and location of GPR30 and ERα36 in breast and endometrial cancer cells. We also investigated their possible roles in cancer cell migration. Using a combination of cell migration assays, gene silencing siRNAs, actin polymerisation measurements and immuno-fluorescence we have demonstrated that SKBr3 cells (a ER receptor negative, breast cancer cell line) migrate towards the GPR30/ERα36 agonist G-1; an effect that is attenuated by G-15, a GPR30/ERα36 antagonist and pERK inhibitors, but not by ROCK inhibitors. We have also demonstrated that G-1 activates a rapid signalling pathway involving changes in the actin cytoskeleton. A similar migration response is seen in endometrial cancer cells. However, we have also discovered that another breast cancer, ER receptor negative cell line, MDA-MB-231, although expressing both GPR30 and ERα36 does not display this migratory behaviour. We propose and provide evidence that the migratory signalling pathway via GPR30 and ERα36 involves the activation of the HER 2 receptor which the MDA-MB-231 cell line lacks. These findings may progress the development of new therapeutics targeting ER negative breast cancer tumors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Breast ; Endometrium