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.