Anti-Müllerian hormone: A missing link in prostate cancer?

Abstract

Prostate cancer is the most frequently diagnosed cancer in men in many countries including the USA, France, Germany and New Zealand (Health, 2002, Jemal et al., 2008, Ferlay et al., 2010). The growth of human prostate tissue and the development of prostate cancer is an intricate process maintained by the fine balance of a variety of factors including androgens, estrogens, stromal-epithelial interactions, nervous system input and growth factors (Massague, 1987, Moses et al., 1990, Ittman and Mansukhani, 1997, McVary et al., 1998, Giri et al., 1999, Khandwala et al., 2000, Renehan et al., 2004). Anti-Müllerian hormone (AMH) is one growth factor that may be involved in prostate cancer progression.

Previously Segev et al. (2002) showed that AMH inhibits the growth of prostate cancer cells, and Loo et al. (2008) and Segev et al. (2002) showed that its type II receptor (AMHRII) was expressed by the prostate in mice and humans, respectively. Consequently, this project sought to begin to investigate the role of AMH in prostate cancer by examining the localisation and quantifying the expression of AMH propeptide, AMH and AMHRII in benign tissue, low-grade and high-grade cancer of the human prostate using human prostate tissue samples and cells.

Immunohistochemistry was used to determine the localisation of AMH propeptide, AMH and AMHRII in human prostate tissue samples, which included various disease states. Double immunofluorescence was then carried out to confirm the location of AMH and AMHRII in human prostate tissue samples. Assessment of immunoreactivity and Western blot analysis were used to quantify the expression of AMH propeptide, AMH and AMHRII expression in human prostate tissue samples. The localisation and expression of AMH and AMHRII in normal and malignant stromal and epithelial human prostate cells was also determined using immunocytochemistry, Western blot analysis and assessment of immunoreactivity, respectively.

The results of this project show that AMH propeptide, AMH and AMHRII are located in human prostate stroma and epithelium at all stages of disease. Immunohistochemistry and double immunofluorescence of human prostate tissue samples (which included benign tissue, low-grade cancer and high-grade cancer) exhibited AMH propeptide, AMH and AMHRII immunoreactivity of stroma and epithelium. Immunocytochemistry of normal and malignant stromal and epithelial human prostate cells also demonstrated AMH and AMHRII immunoreactivity. Furthermore, Western blot analysis of benign and malignant human prostate tissue samples and cells revealed immunoreactive bands that may correspond to cleaved and uncleaved forms of AMH and AMHRII.

This project also found that there was no significant difference in expression of AMH propeptide or AMHRII in the stroma and epithelium of benign and malignant human prostate tissue samples, as indicated by assessment of immunoreactivity and Western blot analysis. However, there was evidence to suggest that AMH expression is increased in malignancy because AMH immunoreactivity was significantly increased in the epithelium of low-grade and high-grade human prostate tissue samples. Therefore, it seems that AMH may be involved in an autocrine/paracrine growth regulatory mechanism in the human prostate, as has been demonstrated in the human testes (Racine et al., 1998), brain motor neurons (Wang et al., 2005a), and female endometrium (Wang et al., 2009a). This implies AMH may function as a growth-inhibitor (as was indicated by Segev et al.'s (2002) findings on the effect of AMH on prostate cancer cells) or as a growth-stimulator depending on the cellular context.

However, further research is needed to confirm the expression pattern of AMH and AMHRII in human prostate cancer progression, and to investigate the effect of AMH peptide on normal and malignant human prostate cell growth both in vivo and in vitro.