The contribution of growth hormone to mammary neoplasia

Abstract

While the effects of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes to neoplastic progression is more recent. Accumulating literature implicates GH-mediated signal transduction in the development and progression of a wide range malignancies including breast cancer. Recently autocrine human GH been demonstrated to be an orthotopically expressed oncogene for the human mammary gland. This review will highlight recent evidence linking GH and mammary carcinoma and discuss GH-antagonism as a potential therapeutic approach for treatment of breast cancer.

Figure 1. Endocrine, paracrine and autocrine effects of hGH in the mammary gland

The endocrine effects of hGH secreted from the anterior pituitary impact on numerous tissues resulting in postnatal somatic growth. One of the main effects of increased circulating hGH is the induction of hepatic IGF-1 secretion. Both hGH and IGF-1 are essential for mammary gland development. hGH in the pubertal mammary gland influences TEB formation and effects epithelial (orange) stromal and (blue) endothelial (red) cell characteristics through autocrine and paracrine effects.

Figure 2. Autocrine hGH extends the replicative capacity of human mammary epithelial cells (HMECs) in vitro

Stable forced expression of hGH in human primary HMECs (Clonetics) was established (designated HMEC-hGH) while a control cell line was generated by stable transfection with vector alone (designated HMEC-VEC). a) The population doubling (PD) time of these two cell lines in mammary epithelial cell growth medium was calculated from PD27. b) HMEC colony formation in soft agar. HMEC-hGH and - VEC cells were embedded in 0.35% agarose as previously described [19] and allowed to form colonies over 14 days culture in mammary epithelial cell growth medium. HMEC-VEC cells did not form colonies in soft agar.

Figure 3. The role of autocrine hGH in mammary neoplasia

Autocrine hGH influences cell growth and survival, migration and invasion, epitheliomesenchymal transition (EMT), replicative potential and oncogenic transformation through differential regulation of gene expression. Genes known to be upregulated or downregulated by autocrine hGH implicated in oncogenesis are listed.