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PMID:16049981

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Citation

Silvertown, JD, Ng, J, Sato, T, Summerlee, AJ and Medin, JA (2006) H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int. J. Cancer 118:62-73

Abstract

Our study reports a preliminary investigation into the role of human H2 relaxin in prostate tumor growth. A luciferase-expressing human prostate cancer cell line, PC-3, was generated and termed PC3-Luc. PC3-Luc cells were transduced with lentiviral vectors engineering the expression of either enhanced green fluorescent protein (eGFP) or both H2 relaxin and eGFP in a bicistronic format. These transduced cells were termed PC3-Luc-eGFP and PC3-Luc-H2/eGFP, respectively. To gauge effects, PC3-Luc-H2/eGFP and PC3-Luc-eGFP cells were injected into NOD/SCID mice and monitored over 6 weeks. PC-3 tumor xenografts overexpressing H2 relaxin exhibited greater tumor volumes compared to control tumors. Circulating H2 relaxin levels in sera increased with the relative size of the tumor, with moderately elevated H2 relaxin levels in mice bearing PC3-Luc-H2/eGFP tumors compared to PC3-Luc-eGFP tumors. Zymographic analysis demonstrated that proMMP-9 enzyme activity was significantly downregulated in H2 relaxin-overexpressing tumors. An advanced angiogenic phenotype was observed in H2 relaxin-overexpressing tumors indicated by greater intratumoral vascularization by immunohistochemical staining of endothelial cells with anti-mouse CD31. Moreover, PC3-Luc-H2/eGFP tumors exhibited increased VEGF transcript by reverse-transcription PCR, compared to basal levels in control animals. Taken together, our study provides the first account of a potential role of H2 relaxin in prostate tumor development.

Links

PubMed Online version:10.1002/ijc.21288

Keywords

Animals; Cell Proliferation; Genetic Markers; Green Fluorescent Proteins/biosynthesis; Green Fluorescent Proteins/genetics; Humans; Immunohistochemistry; Male; Mice; Mice, SCID; Neovascularization, Pathologic; Phenotype; Prostatic Neoplasms/genetics; Prostatic Neoplasms/pathology; Relaxin/biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Transduction, Genetic; Transplantation, Heterologous; Tumor Cells, Cultured; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:REL2

involved_in

GO:0045766: positive regulation of angiogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:REL2

involved_in

GO:0050790: regulation of catalytic activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:REL2

GO:0045766: positive regulation of angiogenesis

ECO:0000315:

P

In figure 8, the authors demonstrate that tumors, comprised of human prostate tumor cells, had greater microvessel density when made to overexpress human relaxin.

complete
CACAO 2005

HUMAN:REL2

GO:0048552: regulation of metalloenzyme activity

ECO:0000314:

P

In figure 6A, the authors demonstrate that the addition of human relaxin increases the activity of matrix metalloproteinase activity in human prostate tumor cells.

complete
CACAO 2049


See also

References

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