The effect of physiological concentrations of sex hormones, insulin, and glucagon on growth of breast and prostate cells supplemented with unmodified human serum

Abstract

The majority of cell culture studies have assessed the effect of hormones on cancer cell growth using media supplemented with charcoal-treated fetal bovine serum (CTS). We aimed to determine whether using a system more reflective of the human condition by changing the charcoal-treated serum to an untreated pooled human serum (PHS) resulted in the same hormone responses in breast and prostate cell lines. MCF-7 breast cancer, MCF-10A non-transformed breast, and LNCaP prostate cancer cell lines supplemented with PHS were treated with high and low physiological concentrations of six hormones (17β-estradiol, dehydroepiandosterone (DHEA), dihydrotestosterone (DHT), testosterone, insulin, and glucagon). Cell growth was measured after 72 h of incubation. All hormones stimulated growth of MCF-7 cells (p < 0.05). MCF-10A cell growth was inhibited by DHEA, DHT, and testosterone (p < 0.05), unaffected by 17β-estradiol and glucagon, and stimulated by insulin (p < 0.05). LNCaP cell growth was stimulated by the highest concentration of DHEA and DHT (p < 0.05) and inhibited by the highest concentration of 17β-estradiol (p < 0.05), while insulin and testosterone, had no effect. Overall, PHS lowered the magnitude of the effect of hormones on cell growth in comparison to CTS. Due to the presence of all serum constituents, our model represents a more appropriate physiological environment for determining the effect of hormones on cancer cell growth. Further studies are required to determine the mechanisms by which added hormones interact with the constituents of untreated human serum.

Androgen Signaling Promotes Translation of TMEFF2 in Prostate Cancer Cells via Phosphorylation of the α Subunit of the Translation Initiation Factor 2

“…Addition of DHT increased Luciferase expression in a dose-dependent manner (Figure 2A), indicating that androgens stimulate the translation of the main ORF. Importantly, this effect was observed at DHT concentrations within the physiological levels found in human serum [19]. Luciferase activity from cells carrying the pTMXXXX-Gluc reporter construct, in which the AUGs from all four uORFs were mutated, did not change in response to DHT, although, as expected, was much higher (Figure 2A).…”

Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1

“…The prostate gland (PG) is an exocrine gland tightly influenced by the endocrine milieu, as its development and homeostasis is regulated, for instance, by sexual hormones. Indeed, testosterone, the main sexual hormone responsible for prostate homeostasis, can be locally converted to dihydrotestosterone, which is involved in increasing proliferation and reducing death of PG cells . Moreover, a growing body of evidence indicates that the endocrine axis comprising growth hormone (GH), insulin and insulin‐like growth factor 1 (IGF1) is locally expressed in the PG and plays a relevant role in its pathophysiology .…”

5α-Dihydrotestosterone regulates the expression of L-type calcium channels and calcium-binding protein regucalcin in human breast cancer cells with suppression of cell growth

“…The same response pattern was observed for the mRNA expression of RGN in DHT-treated MCF-7 cells (0.34 ± 0.07-fold, 0.36 ± 0.09-fold and 0.48 ± 0.05-fold, respectively, for 1, 10 and 100 nM,Fig. 3d).The 1 nM DHT concentration was chosen for subsequent analysis because it induced changes on the mRNA expression of Ca v 1.2 channel subunit and RGN, and it is in the range of reported serum physiological concentrations in pre-(0.05 nM) and postmenopausal (1.26 nM) women[22].Concerning the expression of Ca v 1.2 channel subunit and RGN proteins, a distinct response was observed upon treatment with DHT. MCF-7 cells treated with 1 nM DHT displayed increased expression of Ca v 1.2 protein at 24 h…”