Abstract

Background: The interaction between pituitary hormones (Growth Hormone-Prolactin), ovarian hormones (Estradiol) and growth factors forms the basis of the mechanisms underlying the growth of tumors of the breast. The literature contains reports of the increased expression of the mitogenic GH (Growth Hormone)/IGF1 (Insulin-Like Growth Factor) axis in tumor tissues compared to healthy tissues, with a directly proportional dose-dependent relationship between GH/IGF1, proliferative index and invasive ability in numerous types of tumors. Methods and Findings: We carried out this experimental research on the mitogenic role of GH and consequently on the rationale of the anticancer use of its inhibition. The levels of expression of several genes, GH and GHR, were evaluated in 39 cases of breast cancer, divided according to different risk levels on the basis of immunohistochemical and histological tests with nuclear grade. Conclusion: Research showed that breast cancers with a high and intermediate risk of recurrence are characterized by over-expression of GH and of its receptor (GHR). The expression was limited in cases with a low risk. The overexpression of GH-GHR in breast cancer with a ratio proportional to the level of aggressiveness is a rationale that can encourage a therapeutic intervention with inhibition of the mitogenic GH-IGF1-PRL axis and estrogen.

Highlights

  • It has been scientifically proven with endocrine, biological and biochemical data [1,2] that the physiological growth mammary glands is stimulated by anterior pituitary hormonegrowth hormone (GH) is a peptide hormone, synthesized, accumulated and secreted by the adenohypophysis

  • Research showed that breast cancers with a high and intermediate risk of recurrence are characterized by over-expression of GH and of its receptor (GHR)

  • The overexpression of GH-GHR in breast cancer with a ratio proportional to the level of aggressiveness is a rationale that can encourage a therapeutic intervention with inhibition of the mitogenic GH-IGF1-PRL axis and estrogen

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Summary

Introduction

It has been scientifically proven with endocrine, biological and biochemical data [1,2] that the physiological growth mammary glands is stimulated by anterior pituitary hormoneGH is a peptide hormone, synthesized, accumulated and secreted by the adenohypophysis. The family of cytokine receptors (Class I) and the family of interferon receptors (Class II) share structural characteristics and common signal transduction pathways with GHR Both classes of receptor are associated with various members of the family of Janus tyrosine kinases (JAK) and activate a new family of transcription factors, known as transcription transducers and activators, which relate ligands to activation of gene expression [7]. The literature contains reports of the increased expression of the mitogenic GH (Growth Hormone)/IGF1 (Insulin-Like Growth Factor) axis in tumor tissues compared to healthy tissues, with a directly proportional dose-dependent relationship between GH/IGF1, proliferative index and invasive ability in numerous types of tumors. Estrogen and GH are essential for breast development at puberty; prolactin stimulates the mammary glands to produce milk

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