Endocrine Abstracts

Although not normally considered an oestrogen responsive tissue, compelling evidence now exists suggesting that the colon is responsive to oestrogenic effects. Results from the Women’s Health Initiative demonstrated that post-menopausal women taking oestrogen and progestins as hormone-replacement therapy (HRT) had a 40% reduction in developing colorectal cancer (CRC). Intriguingly, patients taking oestrogen supplements at the time of CRC diagnosis presented a much more ad...

Many post-doctoral scientists still believe that the road to academic success follows the traditional university career trajectory. Although some lectureship and fellowship positions will inevitably be filled by those who have chosen this path, forward-thinking universities now seek principal investigators who have international collaborations and industry links, supported by unique expertise and knowledge on many divergent aspects of scientific research. But as the economic d...

Colorectal cancer (CRC) is the third most common cancer and is one of the highest incidences and mortality tumours worldwide. Our group has previously shown that CRC favours oestradiol synthesis by increasing steroid sulfatase (STS) activity and altering 17β-hydroxysteroid dehydrogenases (HSD17Bs) expression. However, what regulates STS activity and HSD17Bs expression and activity in CRC remains unknown. In breast and prostate cancer inflammatory mediators, such as TNF&#9...

Oestrogens impact colorectal cancer (CRC) development and proliferation. Biologically active oestrogens, oestrone (E1) and oestradiol (E2), are metabolised through hydrolysis of their sulfated forms (oestrone sulfate (E1S) and oestradiol sulfate) by steroid sulfatase (STS). We have shown that increased STS activity drives CRC proliferation via oestrogen hydrolysis. We have also identified that CRC expresses the necessary organic anion transport...

The production of oestradiol (E2) is paramount for the growth of oestrogen receptor α positive breast cancer. Various strategies have been used, including the use of enzyme inhibitors against either aromatase (AROM) or steroid sulphatase (STS), in an attempt to ablate E2 levels. Both these enzymes play a critical role in the formation of oestrogenic steroids (see figure 1) and their inhibitors are now showing success in the clinic. The studies presented here demonstrate t...

Circulating oestrogen concentrations affect the incidence of and outcomes for patients with colorectal cancer (CRC). We have previously shown that steroid sulphatase (STS), the fundamental enzyme that liberates conjugated oestrogens into their active forms, is significantly elevated in human CRC tissue. Here we demonstrate that elevated STS activity correlates to increased CRC proliferation, and that these effects are mediated through G-protein coupled oestrogen receptor (GPER...

Oestrogenic effects on colorectal cancer (CRC) incidence, proliferation, and patient survival remains controversial. We have previously shown enzymic pathways favouring oestradiol (E2) synthesis are upregulated in CRC, and stimulation of the G-protein coupled oestrogen receptor (GPER) by E2 increases CRC proliferation. Here we interrogated The Cancer Genome Atlas (TCGA) Colon Adenocarcinoma (COAD) database to determine all oestrogen metabolism enzymes and...

Oestrogenic effects on colorectal cancer (CRC) incidence, proliferation, and patient survival remains controversial. We have previously shown enzymic pathways favouring oestradiol (E2) synthesis are upregulated in CRC, and stimulation of the G-protein coupled oestrogen receptor (GPER) by E2 increases CRC proliferation. Here we interrogated The Cancer Genome Atlas (TCGA) Colon Adenocarcinoma (COAD) database to determine all oestrogen metabolism enzymes and...

Colorectal cancers (CRC) represent 9.4% of all cancers, with about 42 000 new UK cases per year. Current treatment involves surgical resection followed by radio- and chemo-therapy. 5-Fluorouracil is the standard post-operative chemotherapy although tolerance is poor due to dose-limiting toxicities and drug-resistance. New treatment strategies are therefore sorely needed. One emerging chemotherapeutic option is to target oestrogen metabolism. Our novel work rev...

Colorectal cancer (CRC) is the 2nd most commonly diagnosed cancer in Europe. Previously, we have shown steroid sulphatase (STS), the enzyme that converts conjugated oestrogens to their active forms, is significantly upregulated in human CRC tissue. Furthermore, increased STS activity substantiates greater CRC tumour burden in mouse models. Here we demonstrate that this oestrogen-induced increase of CRC proliferation is mediated by G-protein coupled oestrogen receptor (GPER) vi...