Endocrine Abstracts

Antagonists of growth hormone-releasing hormone (GHRH-ant) may exert their antiproliferative effects directly on cancer cells, which are mediated by the tumoral GHRH receptors identified by us. Furthermore we showed that GHRH-ant are able to induce apoptosis in LNCaP human prostate cancer cells through a Ca2+-dependent pathway. However, the molecular features involved in the antiproliferative effect of GHRH-ant have not yet been elucidated. To study this, gene expression profile of LNCaP cancer cells treated with a GHRH-ant MZ-J-138 (10 μM) for 1, 5 or 18 hours was analyzed and compared to that of untreated control LNCaP cells. The genome-wide cDNA microarray chip type in the experiment was Illumina Human HT-12 v.4 Expression BeadChip. Expression profiling showed 181, 152, 16 up-regulated genes and 98, 43, 8 down-regulated genes in LNCaP cells treated with GHRH-ant for 1, 5, 18 hours, respectively (average fold difference >1.5; P<0.0001). We observed overexpression of PMEPA1, BRCA1, KLF6, FANCG, RBL1, E2F2 and down-regulation of SLC45A3, TMPRSS2, MYC in LNCaP cells after treatment with GHRH-ant. In addition, many cell cycle genes are constituently activated in treated LNCaP cells. The up-regulated negative regulators of cell proliferation and the down-regulation of some factors expressed in high concentration in prostate cancer cells may explain why GHRH-ant can reduce cell proliferation of LNCaP cells. Our data suggest also the involvement of p53-dependent and independent mechanisms in the antiproliferative effect of GHRH-ant. Treatment with GHRH-ant may offer a new approach to the therapy of prostate and other hormone-sensitive cancers (supported by OTKA K 068452).

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.