High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland

Abstract

We have demonstrated and localized human GH (hGH) gene expression in surgical specimens of normal human mammary gland and in proliferative disorders of the mammary gland of increasing severity using sensitive in situ RT-PCR methodology. hGH mRNA identical to pituitary hGH mRNA was first detected by RT-PCR of RNA derived from samples of normal human mammary gland. Cellular localization of hGH gene expression in the normal mammary gland exhibited restriction to luminal epithelial and myoepithelial cells of the ducts and to scattered stromal fibroblasts. We subsequently examined the expression of the hGH gene in three progressive proliferative disorders of the human mammary gland, i.e. a benign lesion (fibroadenoma), a pre-invasive stage (intraductal carcinoma) and an invasive ductal carcinoma. hGH mRNA was readily detected in the tumoral and nontumoral epithelial components and also in cells of the reactive stroma including fibroblasts, myofibroblastic and myoepithelial cells, inflammatory infiltrate lymphocytes and endothelial cells in areas of neovascularization. In all three proliferative disorders examined, the intensity of the cellular labeling observed in both the epithelial and stromal compartments was always stronger compared with that in adjacent normal tissue. hGH protein was also present in significantly higher concentration in extracts derived from proliferative disorders of the mammary gland compared with extracts derived from normal mammary gland. We also examined hGH gene expression in axillary lymph nodes not containing and containing metastatic mammary carcinoma. hGH gene expression was evidenced in metastatic mammary carcinoma cells and in reactive stromal cells by both in situ hybridization and in situ RT-PCR. In contrast, in lymph nodes not containing metastatic mammary carcinoma, hGH mRNA was detected only by use of in situ RT-PCR. Thus, increased expression of the hGH gene in the epithelial component and the de novo stromal expression in proliferative disorders of the mammary gland are suggestive of a pivotal role for autocrine hGH in neoplastic progression of the mammary gland.

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

“…Patients with breast cancer exhibit increased serum concentrations of GH (42) and IGF-I (43), and autocrine production of human GH increases cell numbers in mammary carcinoma as a consequence of both increased mitogenesis and decreased apoptosis (44,45). Increased expression of GH with respect to normal mammary gland has been associated with proliferative disorders, including invasive ductal carcinoma (46). In the case of PRL, it has been reported that as many as 44% of patients with metastatic breast disease have been hyperprolactinaemic at some stage during the course of the disease (47), and the presence of bioactive PRL in human breast cancer cells acts in an autocrine manner to stimulate cell proliferation (48).…”

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

“…A particular and essential role for neoplasia progression of autocrine production of Prl has been revealed [34,38] . Only autocrine, but not exocrine GH, is suggested to promote neoplasia [39][40][41] .…”

Growth hormone (GH) modulation of Epidermal growth factor (EGF) signalling in human mammary epithelial cells

“…GH overexpression is associated with proliferative diseases in animals and humans (Raccurt et al, 2002). Acromegalic patients have an increased risk for developing cancer (Webb et al, 2002;Jenkins, 2004;Siegel and Tomer, 2005).…”