Human relaxin-2: historical perspectives and role in cancer biology

Nair, Vinojini B.; Samuel, Chrishan S.; Separovic, Frances; Hossain, Mohammed Akhter; Wade, John D.

doi:10.1007/s00726-012-1375-y

Cited by 33 publications

(19 citation statements)

References 84 publications

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“…While the accuracy of porcine RLX (100 ng/ml) was confirmed, since it decreased the contractions of myometrial strips from swine ( Figure 2E). The lack of effect of porcine RLX on bovine myometrium has been surprised, since it had used to study effect on E2, OT and P4 secretion [34,41] and to cause a cervical dilatation [34,42] in beef heifers in vivo, as well as cow RLX preparations gave reactions of identity with the porcine RLX [43]. Therefore, it is suggest that RLX from swine and human is not appropriate to use as a support of in vitro model to study the effect of xenobiotics on myometrial contractions.…”

Section: Results With Discussionmentioning

confidence: 99%

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The Preliminary Study About the Involvement of Relaxine in Adverse Effect of Polychlorinated Biphenyls on Bovine Myometrial Contractions

Wrobel¹

2017

J Clin Mol Endocrinol

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Polychlorinated biphenyls (PCBs) are a group of synthetic xenobiotics, which were used in lots of industrial applications. Two individual congers (PCB 153 and PCB 77) belong to the most prominent environmental contaminations among PCBs, but they have opposite type of configuration and therefore they can exert a different way of action. Since PCBs increased the force of myometrial contractions, in this work, their effect on myometrial sensitivity on inhibitor of myometrial contractions (relaxine, RLX) was studied.Bovine myometrial cells and strips, and luteal cell at 4-8 month of pregnancy, were obtained accidentally in commercial abattoir. They were treated by PCB 153 and PCB 77 and mRNA expression of RLX receptor in myometrial cells and contractions of myometrial strips as well as the secretion of progesterone (P4) and oxytocin (OT) from luteal cells, were measured under their effect.Both studied congeners decreased (P<0.05) the mRNA expression of RLX receptor in myometrium. Admittedly, both PCB 77 and 153 increased (P<0.05) the basal force of contractions, while RLX showed any effect on myometrial contractions. Studied PCBs increased also (P<0.05) secretion of P4 and OT from luteal cells.It is suggested that PCBs can decreased the sensitivity of myometrium on RLX but their direct effect on RLX function have to be further investigated. Keywords: Endocrine Disruption; Pregnancy; Uterus IntroductionPolychlorinated biphenyls (PCBs) are a group of synthetic, chlorinated aryl hydrocarbons, which were extensively used in lots of industrial applications, mainly in transformers, capacitors or as hydraulic fluids, heat exchange liquids as well as plasticizers and others [1]. Because of different degree of chlorination, there are possible up to 209 congeners of PCBs. Among them, 3,3 ' ,4,4 ' -tetrachlorobiphenyl (PCB 77) is one of the most abundant PCB congeners in human milk. This congener is a non-ortho chlorine substituted with coplanar configuration and appear to exert its toxic effects via interacting with the cytosolic aryl hydrocarbon receptor (Ahr). Hence is recognized also as dioxin-like PCBs [2]. Since PCB 77 can affect the cell also through estrogen [3] and glucocorticoid receptors [4], it is recognized as a significant environmental pollutant and endocrine disruptor [3] with a wide spectrum of way of action. Admittedly 2,2',4,4', 5,5'-hexachlorobiphenyl PCB 153 is also one of the most prominent environmental contaminants, but oppositely to PCB 77 is classified as di-ortho, non-coplanar, non-dioxin congener of PCBs [5] and is known to have rather estrogenic properties [6]. Even though PCBs production and use were banned in USA and Europe more than three decades ago, they are still measured in environment [7]. Due to their lipophilic nature and resistance for biodegradation, PCBs have been bio-accumulated in animal tissues [8], also in domestic animals [9,10]. Therefore PCBs have been also measured in food samples [11] and they can be mentioned as a serious health risk.Since PCBs accumulation in preg...

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Section: Results With Discussionmentioning

confidence: 99%

“…It was porcine RLX (30, 60 and 100 ng/ml, according to Kaczmarek et al [32], it is 200-500 ng/ml) since it was also used in study in beef heifers in vivo [29,33]. Since signaling by Relaxin-2 human through its target receptors enhances the growth of pubic ligaments and ripening of the cervix during birth [34] it was also used in this study (10-400 ng/ ml). …”

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confidence: 99%

The Preliminary Study About the Involvement of Relaxine in Adverse Effect of Polychlorinated Biphenyls on Bovine Myometrial Contractions

Wrobel¹

2017

J Clin Mol Endocrinol

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“…ILK is a β1integrin cytoplasmic domain interacting protein, and functions as a scaffold in forming multiprotein complexes connecting integrins to the actin cytoskeleton and signaling pathways, which is involved in the various oncogenic pathways related to cell proliferation, invasion, migration and angiogenesis (17). Some functions of RLN2 in carcinogenesis have been suggested, but remain to be investigated (18).…”

Section: Down-regulation Of Lmo1 Suppressed the Expression Of Lims1mentioning

confidence: 99%

Chromatin Immunoprecipitation and DNA Sequencing Identified a LIMS1/ILK Pathway Regulated by LMO1 in Neuroblastoma

Saeki¹,

Saito

Sugaya

et al. 2018

CGP

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“…It is well-known that three peptide forms of RLN: RLN1, RLN2, and RLN3, exist in humans, although the roles of two of the peptides, RLN1 and RLN3, remain unclear [12]. RLN2, which is produced in male prostate tissue [13], and female corpus luteum tissue [14,15] is known as a major human circulating RLN [12,16]. The effects of RLN have been established in female reproduction and pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Relaxin 2/RXFP1 Signaling Induces Cell Invasion via the β-Catenin Pathway in Endometrial Cancer

Fue

Miki

Takagi

et al. 2018

IJMS

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Relaxin is known to play an important role in animal pregnancies, including those of humans. It is suggested that relaxin induces aggressive cell growth and invasiveness in several types of cancer, including endometrial cancer. However, the mechanisms of relaxin remain largely unclear. In this study, we examined the effects of relaxin 2 (RLN2), the major circulating relaxin in humans, on human endometrial carcinoma cell lines. RLN2 treatment induced invasion in HEC-1B and Ishikawa cells. RLN2-induced cell invasion was significantly decreased by transfection of relaxin receptor 1 (RXFP1) siRNAs. The β-catenin inhibitor, XAV939, also significantly inhibited the RLN2-induced cell invasions. Both a decrease of cadherin expression and an increase of β-catenin phosphorylation were observed in response to the RLN2 treatment in HEC-1B and Ishikawa cells. We then examined RLN2 and RXFP1 expression in 80 human endometrioid endometrial carcinoma tissues. RLN2 immunoreactivity was detected in the human endometrial carcinoma cells and had a correlative tendency with histological grade and RXFP1. These results suggest that adherens junctions in cancer cells are weakened by the breakdown of the cadherin/catenin complex, which is induced by β-catenin phosphorylation via RLN2/RXFP1 signaling.

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Human relaxin-2: historical perspectives and role in cancer biology

Cited by 33 publications

References 84 publications

The Preliminary Study About the Involvement of Relaxine in Adverse Effect of Polychlorinated Biphenyls on Bovine Myometrial Contractions

The Preliminary Study About the Involvement of Relaxine in Adverse Effect of Polychlorinated Biphenyls on Bovine Myometrial Contractions

Chromatin Immunoprecipitation and DNA Sequencing Identified a LIMS1/ILK Pathway Regulated by LMO1 in Neuroblastoma

Relaxin 2/RXFP1 Signaling Induces Cell Invasion via the β-Catenin Pathway in Endometrial Cancer

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