Relaxin-like factor (RLF) is differentially expressed in the normal and neoplastic human mammary gland

Hombach‐Klonisch, Sabine; Buchmann, J; Sarun, Sukhéna; Fischer, Bernd; Klonisch, Thomas

doi:10.1002/1097-0142(20001201)89:11<2161::aid-cncr3>3.0.co;2-k

Cited by 42 publications

(26 citation statements)

References 41 publications

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“…In the female, the relaxin peptide is a factor associated with the physiological development and neoplastic growth of the human mammary gland (2,3). Indeed, the human-1, human-2, and relaxin-like factor (or INSL3) peptides have been shown to be up-regulated in human neoplastic mammary tissues (2,4). A number of studies suggesting the potential roles of relaxin in cancer have reported this peptide to be involved in tumor cell growth and differentiation (5)(6)(7), the promotion of tumor neovascularization and angiogenesis via the possible up-regulation of nitric oxide synthase (8,9), and vascular endothelial growth factor (10,11).…”

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confidence: 99%

Adenovirus-Mediated Expression of Human Prorelaxin Promotes the Invasive Potential of Canine Mammary Cancer Cells

2003

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This study reports the characterization of a recombinant adenoviral vector containing a tetracycline-regulatable promoter, driving the bicistronic expression of the human H2 preprorelaxin (hH2) cDNA and enhanced green fluorescent protein, via an internal ribosomal entry site. An hH2 ELISA was used to measure the secreted levels of recombinant hH2 in transfected canine (CF33.Mt) and human (MDA-MB-435) mammary cancer cell lines over a 6-d period; secreted peptide peaked on d 2 and 4 for the canine and human cell types, respectively. An unprocessed hH2 immunoreactive form of approximately 18 kDa was identified by Western blotting analysis and confirmed by mass spectrometry, suggesting that prorelaxin remains unprocessed in these cell types. The biological activity of the adenovirally expressed human prorelaxin was measured in the established human monocytic cell line THP-1 cAMP ELISA and in an in vitro Transwell cell migration system. Exogenous recombinant hH2 and adenovirally-mediated delivery of prorelaxin to CF33.Mt cells conferred a significant migratory action in the cells, compared with controls. Cell proliferation assays were performed to discount the possibility that the effect of relaxin was mitogenic. Thus, we have demonstrated that prorelaxin has the ability to facilitate cell migration processes exclusive of its ability to stimulate cell proliferation. In validating this adenovirus-based system, we have created a potential tool for further exploration of the physiology of relaxin in mammalian systems.

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confidence: 99%

Adenovirus-Mediated Expression of Human Prorelaxin Promotes the Invasive Potential of Canine Mammary Cancer Cells

2003

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“…Despite early reports of INSL3 expression being restricted to the testis, in 1995 INSL3 mRNA was also detected in human cyclic corpus lutea and trophoblast [37]. Thereafter INSL3 was detected in tissues of several species including human mammary gland [38], marmoset [39], mouse [40], and ovine and bovine ovary [41,42].…”

Section: Insl3mentioning

confidence: 90%

Relaxin family peptide systems and the central nervous system

Callander

Bathgate

2010

Cell. Mol. Life Sci.

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Since its discovery in the 1920s, relaxin has enjoyed a reputation as a peptide hormone of pregnancy. However, relaxin and other relaxin family peptides are now associated with numerous non-reproductive physiologies and disease states. The new millennium bought with it the sequence of the human genome and subsequently new directions for relaxin research. In 2002, the ancestral relaxin gene RLN3 was identified from genome databases. The relaxin-3 peptide is highly expressed in a small region of the brain and in species from teleost to primates and has both conserved sequence and sites of expression. Combined with the discovery of the relaxin family peptide receptors, interest in the role of the relaxin family peptides in the central nervous system has been reignited. This review explores the relaxin family peptides that are expressed in or act upon the brain, the receptors that mediate their actions, and what is currently known of their functions.

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“…Investigations using mouse-monoclonal anti-relaxin antibodies and N-methyl-N-nitrosourea as a carcinogen in pregnant rats did not support the hypothesis of relaxin being a cancer-protective factor in the breast [79]. In contrast, the up-regulation of INSL3 peptide in mammary epithelial cells of human neoplastic mammary tissues [5] and the increased expression of both human relaxin isoforms in breast cancer tissues point towards a cancer-promoting role for relaxin-like peptides in the breast.…”

Section: Mammary Glandmentioning

confidence: 90%

“…Immunoreactive relaxin was present in lobular and ductal mammary epithelial cells and myoepithelial cells of normal human breast tissue derived from prepubertal, cyclic, gestational, lactational and postmenopausal women [9,11,12]. In addition, the localization of immunoreactive INSL3 and INSL3 transcripts in the lobular and ductal epithelium of normal postpubertal human breast tissues identified the mammary epithelium as the site of INSL3 production in the breast [5]. Although the potential functions for relaxin and INSL3 in the mammary gland are largely unknown, the expression of both peptides within the mammary epithelium suggests a role for relaxin and INSL3 in the normal physiology of the mammary gland.…”

Section: Mammary Glandmentioning

confidence: 93%

“…The myelomonocytic leukaemia cell line THP-1 was introduced as relaxin-responsive cancer cell line and continues to serve as a suitable model for the study of relaxin-mediated signalling events [1][2][3][4]. Both relaxin-like peptide members, relaxin and INSL3, have been reported in a wide variety of human tumors, including malignancies of the breast, gastrointestinal tract, thyroid gland, lung, and the reproductive system [5][6][7][8][9][10][11][12]. Whereas INSL3 is reduced in testicular Leydig cell adenomas, the expression and production of INSL3 and relaxin are increased in carcinoma tissues of the prostate, the mammary gland and the thyroid suggesting a functional role for these peptides in neoplastic epithelial cells of different origin.…”

Section: Introductionmentioning

confidence: 99%

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Relaxin-Like Peptides in Neoplastic Lesions

Klonisch¹,

Hoang-Vu²,

Hombach‐Klonisch³

2005

CMCIEMA

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The two members of the relaxin family of insulin-like peptide hormones, relaxin and INSL3, and their cognate G protein coupled receptors LGR7 and LGR8, respectively, are present in human tumor tissues. Although the physiological role and signal transduction pathways engaged by relaxin-like members in tumor tissues are still largely unknown, novel data mainly obtained from in-vitro cellular models suggest that relaxin-like peptides influence cellular functions associated with motility and migration, cytoskeletal rearrangement and enzyme production and secretion. The expression of relaxin-like peptides appears to be regulated in a tumor-specific context by the actions of various nuclear receptors. This review summarizes most recent findings on the potential functions of relaxin/ INSL3 ligand-receptor systems in tumor tissues and follows an organ-specific approach.

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Relaxin-like factor (RLF) is differentially expressed in the normal and neoplastic human mammary gland

Cited by 42 publications

References 41 publications

Adenovirus-Mediated Expression of Human Prorelaxin Promotes the Invasive Potential of Canine Mammary Cancer Cells

Adenovirus-Mediated Expression of Human Prorelaxin Promotes the Invasive Potential of Canine Mammary Cancer Cells

Relaxin family peptide systems and the central nervous system

Relaxin-Like Peptides in Neoplastic Lesions

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