Androgen receptors in human melanoma cell lines IIB-MEL-LES and IIB-MEL-IAN and in human melanoma metastases

Abstract

The presence and characteristics of androgen receptors (ARs) have been described by our group in one human melanoma cell line. We have now investigated their presence in two other human melanoma cell lines, IIB-MEL-LES and IIB-MEL-IAN, as well as in biopsies from human metastatic melanoma. Scatchard analysis revealed a single binding component for both cell lines, the apparent dissociation constant obtained being 15 nM, with a binding capacity of 280 fmol/mg total cell protein, for IIB-MEL-LES cells and 14 nM, with a binding capacity of 206 fmol/mg total cell protein for IIB-MEL-IAN cells. When specificity was assessed, not only androgen and anti-androgen but also non-androgenic compounds were able to compete for [3H]R1881 binding, as seen before. When immunocytochemistry of IIB-MEL-LES and IIB-MEL-IAN cells was performed for ARs, both cell lines were deeply stained in the nucleus, whereas no staining was found for oestrogen or progesterone receptors. Every specimen of melanoma metastases tested for the presence of ARs was deeply stained, and in the majority the intensity of the staining was high. Several hormones and anti-hormones were tested for their ability to affect cell proliferation. In both cell lines, testosterone, dihydrotesterone, oestradiol and progesterone significantly stimulated cell proliferation, and this was reversed by hydroxyflutamide, bicalutamide or tamoxifen.

The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region

“…(4) AR positively regulates MMP9 in other cancers, including gastric, bladder, and prostate cancers (Ergun et al, 2007; Hara et al, 2008; Wang et al, 2013; Wu et al, 2010; Zhang et al, 2014). Notably, (5) melanomas express AR (Allil et al, 2008; Morvillo et al, 2002). …”

“…In the years since this study, other studies have confirmed that females have a significant survival advantage compared to males (38%), fewer and delayed metastases, longer delay before relapse, and higher cure rates than males, strongly suggesting a biological basis for the observed gender bias (Bidoli et al, 2012; de Vries et al, 2007; Fisher and Geller, 2013; Gamba et al, 2013; Geller et al, 2002; Joosse et al, 2012; Joosse et al, 2011; Schwartz et al, 2002; Swetter et al, 2009). Differences in expression or activity of sex-hormone receptors, including the estrogen receptor or AR, have long been considered a plausible explanation for the melanoma gender bias (de Giorgi et al, 2011; Morvillo et al, 2002). Recent studies favor a deleterious role for AR and androgens in melanoma, as (1) the female advantage persists even in post-menopausal women, suggesting against an estrogen-related advantage (de Vries et al, 2008; Joosse et al, 2011; Micheli et al, 2009) and (2) there is an increased risk of melanoma following prostate cancer, and vice-versa, suggesting an AR-based connection between the two cancers (Li et al, 2013b; Spanogle et al, 2010).…”

Sex Is an Independent Prognostic Indicator for Survival and Relapse/Progression-Free Survival in Metastasized Stage III to IV Melanoma: A Pooled Analysis of Five European Organisation for Research and Treatment of Cancer Randomized Controlled Trials

“…This trait results in sex differences in survival and progression across the whole spectrum of the disease, from early to late stages. 30 Further research is needed to confirm or exclude any of these hypothetical biologic explanations. 25 However ER-␤ expression declines after menopause 25 and therefore the ER-␤ hypothesis dictates that in postmenopausal women, the advantage over men should decline or even disappear.…”

Challenging Problems in the Surgical Management of Melanoma

“…However, a subsequent study showed that metastatic melanoma tissue specimens were positive for testosterone receptors, which, when activated, stimulate proliferation. These receptors also appeared to be activated by estrogen, and tamoxifen blunted the proliferative effect of estrogen on these receptors [Morvillo et al, 2002]. Importantly, the use of oral contraceptives (OCP) or hormone replacement therapy (HRT) did not appear to increase the risk of melanoma or worsen the prognosis of melanoma [Durvasula et al, 2002;MacKie, 1999;Pfahlberg et al, 1997].…”