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


METHODS
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.
Chatzistamou
Ioulia
I
Department of Pathology, Aretaieion University Hospital, Athens 115 27, Greece.
Schally
Andrew V
AV
Kiaris
Hippokratis
H
Politi
Ekaterini
E
Varga
Jozsef
J
Kanellis
George
G
Kalofoutis
Anastasios
A
Pafiti
Agatha
A
Koutselini
Helen
H
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D019898:Autocrine Communication; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018013:Receptors, Neuropeptide / Q000235:genetics* / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics* / Q000378:metabolism
D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor