Immunohistochemical detection of GHRH and its receptor splice variant 1 in primary human breast cancers

Ioulia Chatzistamou, Andrew V. Schally, Hippokratis Kiaris, Ekaterini Politi, Jozsef Varga, George Kanellis, Anastasios Kalofoutis, Agatha Pafiti, Helen Koutselini

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Objective: CHRH is secreted by the hypothalamus and, upon binding to specific GHRH receptors in the pituitary, stimulates growth hormone (GH) production and release from the pituitary. In addition to this neuroendocrine action, accumulated evidence implies additional roles for GHRH in carcinogenesis in non-pituitary tissues. In vitro and in vivo studies have shown that splice variant 1 (SV1) of the GHRH receptor, which is widely expressed in non-pituitary tissues and cancers, can mediate the proliferative effects of GHRH. The aim of the present study was to investigate the operation of an autocrine stimulatory loop between GHRH and SV1 in primary breast tumors. Design: Fifty-three primary breast tumors were evaluated for GHRH and SV1 expression. Methods: Expression of GHRH and SV1 was assessed by immunohistochemistry using anti-GHRH SV95 and anti-SV1 2317/5 polyclonal antibodies. Results: About 40% of the specimens tested express GHRH and/or SV1 (approx. 25% each), while in 35% of these positive specimens co-expression of these antigens was detected (P < 0.01). Furthermore, a correlation of GHRH, but not SV1, expression was detected in lobular compared with ductal carcinomas. Conclusions: These results constitute the first demonstration for the expression of GHRH and SV1 in primary breast cancers, and provide evidence for the operation of an autocrine stimulatory loop between GHRH and SV1 in primary cancers. Our findings indicate that GHRH analogs could have diagnostic and therapeutic applications for the management of breast cancer.

Original languageEnglish (US)
Pages (from-to)391-396
Number of pages6
JournalEuropean Journal of Endocrinology
Volume151
Issue number3
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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