HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Knocking down gene expression for growth hormone-releasing hormone inhibits proliferation of human cancer cell lines.

Abstract
Splice Variant 1 (SV-1) of growth hormone-releasing hormone (GHRH) receptor, found in a wide range of human cancers and established human cancer cell lines, is a functional receptor with ligand-dependent and independent activity. In the present study, we demonstrated by western blots the presence of the SV1 of GHRH receptor and the production of GHRH in MDA-MB-468, MDA-MB-435S and T47D human breast cancer cell lines, LNCaP prostate cancer cell line as well as in NCI H838 non-small cell lung carcinoma. We have also shown that GHRH produced in the conditioned media of these cell lines is biologically active. We then inhibited the intrinsic production of GHRH in these cancer cell lines using si-RNA, specially designed for human GHRH. The knocking down of the GHRH gene expression suppressed the proliferation of T47D, MDA-MB-435S, MDA-MB-468 breast cancer, LNCaP prostate cancer and NCI H838 non-SCLC cell lines in vitro. However, the replacement of the knocked down GHRH expression by exogenous GHRH (1-29)NH(2) re-established the proliferation of the silenced cancer cell lines. Furthermore, the proliferation rate of untransfected cancer cell lines could be stimulated by GHRH (1-29)NH(2) and inhibited by GHRH antagonists MZ-5-156, MZ-4-71 and JMR-132. These results extend previous findings on the critical function of GHRH in tumorigenesis and support the role of GHRH as a tumour growth factor.
AuthorsN Barabutis, A V Schally
JournalBritish journal of cancer (Br J Cancer) Vol. 98 Issue 11 Pg. 1790-6 (Jun 03 2008) ISSN: 1532-1827 [Electronic] England
PMID18506184 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • MZ 4-71
  • MZ 5-156
  • RNA, Small Interfering
  • Sermorelin
  • Growth Hormone-Releasing Hormone
Topics
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Growth Hormone-Releasing Hormone (analysis, antagonists & inhibitors, genetics, physiology)
  • Humans
  • Male
  • Neoplasms (pathology, therapy)
  • RNA, Small Interfering (genetics)
  • Radioimmunoassay
  • Sermorelin (analogs & derivatives, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: