Specific Binding of Prostaglandin E2 to Membrane Preparations from Human Skin: Receptor Modulation by UVB-Irradiation and Chemical Agents

Lord, Jonathan T.; Ziboh, Vincent A.

doi:10.1111/1523-1747.ep12550453

Cited by 24 publications

(4 citation statements)

References 31 publications

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“…This pattern of expression has been previously observed in the epidermis 21 and similarly reported in crude rat skin subcellular membrane preparations by radioligand binding. 22 This dual pattern of expression is similar to the pattern described for COX-1 and -2. 23,24 In the skin, EP1 expression is believed to play a role in keratinisation.…”

Section: Discussionsupporting

confidence: 73%

Prostanoid receptor EP1 expression in breast cancer

et al. 2008

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Cyclooxygenase enzymes play an important role in carcinogenesis, and increased expression of cyclooxygenase enzymes has been reported in cancers arising at a number of different sites. Most, if not all of these actions are thought to be mediated by prostaglandin E2 (PGE2). The actions of PGE2 are mediated via four main prostanoid receptors, designated EP1, EP2, EP3 and EP4, based on their different pharmacological properties and secondary messenger pathways. Recently, expression of EP1 has been reported in rat mammary gland and the inhibition of this receptor has been documented to have chemopreventive effect in this animal model. EP1 has also been shown to decrease the incidence of colon cancer in mouse models. In this study, we analysed the expression of EP1 in normal and malignant breast tissues. Expression of EP1 was analysed in breast (benign and cancer) cell lines by reverse-transcriptase polymerase chain reaction and by western blot analyses. Expression was also analysed by immunohistochemistry in normal breast tissues and in 89 cases of breast cancer. Semiquantitative analysis of the staining was performed. The data were compared with and correlated with other prognostic factors like tumour size, tumour grade, lymph node status, oestrogen receptor, progesterone receptor (PR), HER2/neu and cyclooxygenase-2. EP1 expression was demonstrated in human breast cancer by immunohistochemistry. Expression of EP1 was seen both in the cytoplasm and/or in the nuclear membrane in majority of cases. Nuclear EP1 expression correlated with PR (P ¼ 0.032) and inversely with node positivity (P ¼ 0.025). However, EP1 expression did not correlate with expression of cyclooxygenase-2 (P ¼ 0.059). Expression of EP1 is frequently seen in human breast cancers. Nuclear expression of EP1 correlates with good prognosis markers like node negative status and PR expression. Keywords: breast cancer; EP1 receptor; cyclooxygenase; PGE2; prostanoid receptor; immunohistochemistry Breast cancer is one of the most common malignancies in developed countries including USA, and the second leading cause of cancer-related deaths in women. 1 As the incidence of breast cancer is increasing, several attempts at testing various preventive agents have been made (reviewed by Arun and Hortobagyi 2 ). Nonsteroidal anti-inflammatory drugs (NSAIDs), which act through inhibition of cyclooxygenase enzyme (COX), are one such class of drugs that have been studied for their possible role in breast cancer prevention. Epidemiological studies investigating the relationship between NSAID use and breast cancer have reported conflicting results; some studies 3-5 show 30-40% reduction in breast cancer incidence with NSAID use, whereas others failed to confirm this relationship. 6,7 NSAIDs work by inhibiting both constitutive and inducible cyclooxygenase enzymes (COX-1 and COX-2, respectively), both of which have been postulated to play a role in carcinogenesis. Elevated cyclooxygenase-2 (COX-2) expression is a marker of poor prognosis in human breast cancer and correla...

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Section: Discussionsupporting

confidence: 73%

Prostanoid receptor EP1 expression in breast cancer

et al. 2008

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“…Significantly, while all normal epidermal samples, AKs, and well-differentiated SCCs exhibit 1+ or greater nuclear scores, a subset of BCCs, spindle cell carcinomas and poorly differentiated SCCs exhibit a lack of nuclear staining, with a statistically significant decrease in nuclear staining noted in BCCs and PD-SCCs (see table 2). It should be noted that PGE 2 receptors have been demonstrated to be localized to intracellular membranes, particularly the nuclear membrane, by multiple methodologies including electron microscopy, immunofluorescence, radioligand binding studies of cellular and intracellular membrane preparations, and immunolocalization of epitope-tagged receptors [14, 33-38]. Moreover, studies using isolated nuclei demonstrated that the receptor is coupled to nuclear calcium signaling [33].…”

Section: Resultsmentioning

confidence: 99%

The EP1 subtype of prostaglandin E2 receptor: Role in keratinocyte differentiation and expression in non-melanoma skin cancer

Konger

Billings

Prall

et al. 2009

Prostaglandins, Leukotrienes and Essential Fatty Acids

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SUMMARY We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation.

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“…In the skin, it has long been known that specific and high affinity binding sites for PGE 2 are located on the membrane fraction of human epidermal cells [13]. With regard to PGE 2 receptors, adult human KCs express mRNA for three subtypes (EP2, EP3, and small amounts of EP4) associated with cAMP signaling [14].…”

Section: Prostanoid Receptor Expression In the Skinmentioning

confidence: 99%

Prostanoids in the cutaneous immune response

Kabashima

2004

Journal of Dermatological Science

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Specific Binding of Prostaglandin E2 to Membrane Preparations from Human Skin: Receptor Modulation by UVB-Irradiation and Chemical Agents

Cited by 24 publications

References 31 publications

Prostanoid receptor EP1 expression in breast cancer

Prostanoid receptor EP1 expression in breast cancer

The EP1 subtype of prostaglandin E2 receptor: Role in keratinocyte differentiation and expression in non-melanoma skin cancer

Prostanoids in the cutaneous immune response

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