A Novel Angiogenic Role for Prostaglandin F2α-FP Receptor Interaction in Human Endometrial Adenocarcinomas

Sales, Kurt J.; List, T; Boddy, Sheila C.; Williams, Alistair; Anderson, Richard A.; Naor, Zvi; Jabbour, Henry N.

doi:10.1158/0008-5472.can-05-0101

Cited by 94 publications

(128 citation statements)

References 44 publications

(56 reference statements)

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“…Moreover, uterine flushings of pregnant pigs contain higher amounts of PGF 2a than those from cyclic animals (Zavy et al 1980). It is likely that this upregulation of conceptus and endometrial PGFS resulting in an increase of PGF 2a in the uterine lumen during implantation could be involved in angiogenesis because PGF 2a signaling mediates expression of angiogenic genes (Sales et al 2005). Nevertheless, the action of PGF 2a in this period should be restricted only to the uterus and conceptus.…”

Section: Role Of Pgs During Pregnancy Establishmentmentioning

confidence: 99%

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Wacławik

2011

Reproduction

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Ovarian progesterone induces essential changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogens secreted by the porcine conceptus on days 11 and 12 of pregnancy provide the initial signal for maternal recognition of pregnancy and maintenance of a functional corpus luteum (CL) for continued production of progesterone. As prostaglandins F 2a (PGF 2a ) and E 2 (PGE 2 ) exert opposing actions on the CL, a tight control over their synthesis and secretion is critical either for the initiation of luteolysis or maintenance of pregnancy. One of the supportive mechanisms by which conceptus inhibits luteolysis is changing PG synthesis in favor of luteoprotective PGE 2 . Conceptus PGE 2 could be amplified by PGE 2 feedback loop in the endometrium. In pigs, as in other species, implantation and establishment of pregnancy is associated with upregulation of expression of proinflammatory factors, which include cytokines, growth factors, and lipid mediators. The conceptus produces inflammatory mediators: interferon g and interferon d, interleukins IL1B and IL6, and PGs, which probably activate inflammatory pathways in the endometrium. The endometrium responds to these embryonic signals by enhancing further progesterone-induced uterine receptivity. Understanding the mechanisms of pregnancy establishment is required for translational research to increase reproductive efficiencies and fertility in humans and animals.

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Section: Role Of Pgs During Pregnancy Establishmentmentioning

confidence: 99%

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Wacławik

2011

Reproduction

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“…A further link of PGF 2a to other features of inflammation has recently been demonstrated, as activation of the FP receptor in endometrial adenocarcinoma led to increased chemokine production and thus increased neutrophil infiltration (Wallace et al 2009). Furthermore, one of the downstream effects of both FP and EP signallings is an increase in COX2 expression (Fujino & Regan 2003, Sales et al 2008b; therefore, this positive feedback loop may further amplify prostaglandin signalling in endometrial adenocarcinoma (Jabbour et al 2005).…”

Section: Prostaglandinsmentioning

confidence: 99%

Inflammatory events in endometrial adenocarcinoma

Wallace

Gibson²,

Saunders

et al. 2010

Journal of Endocrinology

111

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Endometrial adenocarcinoma is the most common gynaecological malignancy in western countries. Many of the established risk factors for developing endometrial cancer are associated with excess exposure to oestrogen unopposed by progesterone. These include nulliparity, late onset of the menopause, post-menopausal hormone replacement therapy and obesity. However, a number of risk factors also promote inflammation, another feature proposed to influence cancer development. The human cycling endometrium undergoes regular and cyclical episodes of inflammation. Moreover, hormonal and genetic changes that occur early in the development of endometrial adenocarcinoma can exacerbate the local inflammatory environment. Via alterations in the expression of local mediators and immune cell function, these may contribute to the development of endometrial cancer. This review discusses the contribution of inflammation to the initiation and progression of endometrial adenocarcinoma. Manipulation of inflammatory pathways may therefore represent a therapeutic target in endometrial adenocarcinoma.

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“…In addition, Ishikawa & Morris (2006) have proposed that an autocrine-amplifying loop that involves COX-2-induced PGE2 and PGF2a production participates in the IL1b-regulated Sertoli cell function. Considering that IL6, PGE2, and PGF2a stimulate ERK1/ 2 in other cell types (Lin et al 2001, Kanda et al 2005, Sales et al 2005, the participation of this pathway in relation to these other hormones, but not to IL1b, cannot be ruled out. However, taking into account that a preincubation with PD98059 or U0126 is necessary to observe the effect of the inhibitors on IL1b stimulation of LDH A mRNA levels, it is tempting to speculate that IL1b itself stimulates an ERK1/2 pathway that is related to the regulation of this biological response.…”

Section: Il1b Regulates Pi3k/pkb and Erk1/2mentioning

confidence: 99%

Participation of phosphatidyl inositol 3-kinase/protein kinase B and ERK1/2 pathways in interleukin-1β stimulation of lactate production in Sertoli cells

Riera

Galardo²,

Pellizzari³

et al. 2007

Reproduction

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Interleukin-1b (IL1b) belongs to a set of intratesticular regulators that provide the fine-tuning of cellular processes implicated in the maintenance of spermatogenesis. The aim of the present study was to analyze the signaling pathways that may participate in IL1b regulation of Sertoli cell function. Sertoli cell cultures from 20-day-old rat were used. Stimulation of the cultures with IL1b showed increments in phosphorylated protein kinase B (PKB), P70S6K, and ERK1/2 levels. A phosphatidyl inositol 3-kinase (PI3K) inhibitor (wortmannin (W)), a mammalian target of rapamycin inhibitor (rapamycin (R)), and a MEK inhibitor (PD98059 (PD)) were utilized to evaluate the participation of PI3K/PKB, P70S6K, and ERK1/2 pathways in the regulation of lactate production by IL1b. PD and W, but not R, decreased IL1b-stimulated lactate production. The participation of these pathways in the regulation of glucose uptake and lactate dehydrogenase (LDH) A mRNA levels by IL1b was also analyzed. It was observed that W decreased IL1b-stimulated glucose uptake, whereas PD and R did not modify it. On the other hand, PD decreased the stimulation of LDH A mRNA levels by IL1b, whereas W and R did not modify it. In summary, results presented herein demonstrate that IL1b stimulates PI3K/PKB-, P70S6K-, and ERK1/2-dependent pathways in rat Sertoli cells. Moreover, these results show that while IL1b utilizes the PI3K/PKB pathway to regulate glucose transport, it utilizes the ERK1/2 pathway to regulate LDH A mRNA levels. This study reveals that IL1b utilizes different signal transduction pathways to modify the biochemical steps that are important to regulate lactate production in rat Sertoli cells.

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A Novel Angiogenic Role for Prostaglandin F2α-FP Receptor Interaction in Human Endometrial Adenocarcinomas

Cited by 94 publications

References 44 publications

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Inflammatory events in endometrial adenocarcinoma

Participation of phosphatidyl inositol 3-kinase/protein kinase B and ERK1/2 pathways in interleukin-1β stimulation of lactate production in Sertoli cells

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