Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo

Fung, Jenny N. T., Jeffery, Penny L., Lee, John D., Seim, Inge, Roche, Deborah, Obermair, Andreas, Chopin, Lisa K. and Chen, Chen (2013) Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo. American Journal of Physiology-Endocrinology and Metabolism, 305 2: E305-E313. doi:10.1152/ajpendo.00156.2013

Author Fung, Jenny N. T.
Jeffery, Penny L.
Lee, John D.
Seim, Inge
Roche, Deborah
Obermair, Andreas
Chopin, Lisa K.
Chen, Chen
Title Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo
Journal name American Journal of Physiology-Endocrinology and Metabolism   Check publisher's open access policy
ISSN 0193-1849
Publication date 2013-07
Year available 2013
Sub-type Article (original research)
DOI 10.1152/ajpendo.00156.2013
Volume 305
Issue 2
Start page E305
End page E313
Total pages 9
Place of publication Bethesda, United States
Publisher American Physiological Society
Collection year 2014
Language eng
Formatted abstract
Ghrelin is a 28-amino acid peptide hormone produced predominantly in the stomach but also in a range of normal cell types and tumors, where it has endocrine, paracrine, and autocrine roles. Previously, we have demonstrated that ghrelin has proliferative and antiapoptotic effects in endometrial cancer cell lines, suggesting a potential role in promoting tumor growth. In the present study, we investigated the effect of ghrelin receptor, GHSR, and gene silencing in vitro and in vivo and characterized ghrelin and GHSR1a protein expression in human endometrial tumors. GHSR gene silencing was achieved in the Ishikawa and KLE endometrial cancer cell lines, using a lentiviral short-hairpin RNA targeting GHSR. The effects of GHSR1a knockdown were further analyzed in vivo using the Ishikawa cell line in a NOD/SCID xenograft model. Cell proliferation was reduced in cultured GHSR1a knockdown Ishikawa and KLE cells compared with scrambled controls in the absence of exogenously applied ghrelin and in response to exogenous ghrelin (1,000 nM). The tumor volumes were reduced significantly in GHSR1a knockdown Ishikawa mouse xenograft tumors compared with scrambled control tumours. Using immunohistochemistry, we demonstrated that ghrelin and GHSR1a are expressed in benign and cancerous glands in human endometrial tissue specimens, although there was no correlation between the intensity of staining and cancer grade. These data indicate that downregulation of GHSR expression significantly inhibits endometrial cancer cell line and mouse xenograft tumour growth. This is the first preclinical evidence that downregulation of GHSR may be therapeutic in endometrial cancer.
Keyword ghrelin
growth hormone secretagogue receptor
endometrial cancer
mouse xenograft tumours
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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