Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation

Konstantinopoulos, Panagiotis A.; Kominea, Athina; Vandoros, Gerasimos P.; Sykiotis, Gerasimos P.; Andricopoulos, P.; Varakis, Ioannis; Sotiropoulou-Bonikou, Georgia; Papavassiliou, A. G.

doi:10.1016/s0959-8049(03)00239-9

Cited by 293 publications

(264 citation statements)

References 22 publications

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“…In addition, further experiments will be important to show whether ERb agonists may not only exert an antiproliferative and pro-apoptotic effect, but also induce differentiation of lymphoid cells. 46 Our results showed that ERb activation by the ERb-selective agonists DPN and KB9520 resulted in both antiproliferative and pro-apoptotic effects in EG7 lymphoid tumors. Also, previous studies have shown pro-apoptotic effects by ERb signaling.…”

Section: Discussionmentioning

confidence: 58%

“…[42][43][44] In the case of breast, colon and prostate cancer, as well as brain astrocytic tumors, ERb expression has been correlated to a higher tumor differentiation grade, in line with its antiproliferative and differentiating effects. [45][46][47][48] It is of interest that malignant lymphoid cells, as described for the cell lines used in this report, retain ERb expression. This may suggest that malignant transformation of cells of lymphoid origin is not generally associated with the loss of ERb expression and therefore remain as useful targets for therapy by ERb agonists.…”

Section: Discussionmentioning

confidence: 99%

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Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

et al. 2011

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Estrogen receptor b (ERb) is expressed in immune cells and studies have suggested an antiproliferative function of ERb. We detected ERb expression in murine T-and human B-cell lymphoma cell lines and analyzed the effects of estradiol and selective ERb agonists on lymphoma growth in culture and in vivo. Treating the cells with estradiol had minor effects on cell growth, whereas the selective ERb agonists diarylpropionitrile (DPN) and KB9520 showed a strong antiproliferative effect. When grafting mice with murine T-cell lymphoma cells, male mice developed larger tumors compared with female mice, a difference that was abolished following ovariectomy, showing estrogen-dependent growth in vivo. To investigate whether lymphoma growth may be inhibited in vivo by ERb agonist treatment, mice grafted with murine lymphoma cells were treated with DPN or KB9520. Both ERb-selective agonists strongly inhibited lymphoma growth. The reduced tumor size seen following either DPN or KB9520 treatment was due to reduced proliferation and increased apoptosis. Our results show an ERb ligand-dependent antiproliferative effect of lymphoma cells expressing endogenous ERb and that lymphoma cell growth in vivo can efficiently be inhibited by ERb agonists. This suggests that ERb agonists may be useful in the treatment of lymphomas.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

et al. 2011

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“…Oestrogen has access to normal colon epithelium, with oestrogen receptor beta (ERb) abundantly expressed in normal colonic epithelia in both genders; however, in CRC cells this expression of ERb is significantly reduced. 42,43 We postulate that the observed age-dependent risk imposed in females by the CC genotype is due to the protective role of oestrogen in younger women.…”

Section: Discussionmentioning

confidence: 99%

An association between the PTGS2 rs5275 polymorphism and colorectal cancer risk in families with inherited non-syndromic predisposition

et al. 2013

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Recently our group completed a genome-wide linkage study investigating Australian and Spanish families with inherited risk of colorectal cancer (CRC). A minor linkage peak from that study located on chromosome 1 correlates with the location of a known CRC risk-modifying gene, prostaglandin synthase (PTGS2). PTGS2 encodes the inducible prostaglandin synthase enzyme cyclooxygenase-2 (COX-2). Prostaglandins are implicated in the initiation of carcinogenesis and progression of tumours. Sequencing of PTGS2 in a small subset of affected individuals identified a high frequency of the minor C allele of single nucleotide polymorphism rs5275. We then genotyped the rs5275 polymorphism in 183 affected and 223 unaffected individuals from our CRC predisposed families. Tests for association in the presence of linkage were made using family-based association tests. The C allele was found to be significantly associated (Po0.01) with diagnosis of hereditary non-syndromic CRC (P ¼ 0.0094, dominant model) and an earlier age of diagnosis (P ¼ 0.0089, heterozygous-advantage model). Interestingly, by stratifying the age of diagnosis data, we observed a speculative gender-discordant effect. Relative to other groups, female CC carriers were diagnosed less when young, but by 60 years of age were the most at risk group. Conversely, CT carriers of both genders showed a consistently earlier diagnosis relative to TT carriers. Our results suggest potential differential age-and genderdependent efficacies of chemopreventative COX-2 inhibitors in the context of non-syndromic colorectal cancer.

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“…This new isoform has been shown by in situ hybridisation techniques 67 to be more widely expressed in colonic epithelium than ER α and is thus felt to be responsible for anti-proliferative estrogenic effects on the colonic mucosa. Higher ER β expression has been shown to confer survival advantage in patients 68 and increase viability in cell lines 69 and lower expression appears to mirror tumour dedifferentiation 70 in human and animal models 71 . Many theories exist as to the mechanism of this protective action of ER β on colonic mucosa and it is probably most likely that the effect is exerted through interaction of a variety of concomitant events-both genomic and non-genomic.…”

Section: Estrogen and Colon Cancermentioning

confidence: 99%

Estrogen and gastrointestinal malignancy

Hogan¹,

Collins²,

Baird³

et al. 2009

Molecular and Cellular Endocrinology

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Summary:The concept that E2 exerts an effect on the gastrointestinal tract is not new and its actions on intestinal mucosa have been investigated for at least three decades. An attempt to consolidate results of these investigations generates more questions than answers, thus suggesting that many unexplored avenues remain and that the full capabilities of this steroid hormone are far from understood. Evidence of its role in esophageal, gastric and gallbladder cancers is confusing and often equivocal. The most compelling evidence regards the protective role conferred by estrogen (or perhaps ERβ) against the development and proliferation of colon cancer. Not only has the effect been described but many mechanisms of action have been explored. It is likely that, along with surgery, chemotherapy and radiotherapy, hormonal manipulation will play an integral role in colon cancer management in the very near future.Introduction:

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Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation

Cited by 293 publications

References 22 publications

Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

An association between the PTGS2 rs5275 polymorphism and colorectal cancer risk in families with inherited non-syndromic predisposition

Estrogen and gastrointestinal malignancy

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