Role of Progesterone in Human Astrocytomas Growth

Abstract

Progesterone (P) participates in the regulation of several reproductive processes such as ovulation and sexual behavior, however, this hormone also participates in non-reproductive processes, such as neural excitability, learning and memory, and pathological processes such as cancer. P mainly elicits its effects by interaction with its intracellular receptor (PR), which is a ligand-activated transcription factor that modifies the expression of genes involved in the control of cell growth and proliferation, such as vascular endothelial growth factor and epidermal growth factor receptor. Two PR isoforms have been reported: PR-B and PR-A, which present different function and regulation. PR isoforms are expressed in U373 and D54 cell lines, which are derived from grades III and IV of human astrocytomas, respectively. In both cells lines P increases the number of astrocytomas cells. The PR antagonist, RU486, blocked P effects and its treatment alone significantly reduced human astrocytomas cell growth in vitro. The over-expression of PR-A in U373 cells significantly reduced P effects. These data suggest that P regulates human astrocytomas cell proliferation through the interaction with PR.

Progesterone Induces the Growth and Infiltration of Human Astrocytoma Cells Implanted in the Cerebral Cortex of the Rat

“…We also observed that RU486 blocked P 4 effects, since rats treated with P 4 + RU486 showed a significant decrease in tumor area in comparison with those treated with P 4 . These data are also consistent with previous reports in astrocytoma cell cultures [23, 26] and suggest that P 4 effects on astrocytoma cell growth occur via the classic mechanism of action, through an interaction with PR.…”

“…The increase in tumor growth after P 4 administration observed in our in vivo conditions is consistent with the results observed in in vitro experiments with U373 cells [23, 26]. Additionally, it has been reported that, in U373 cells, P 4 increases S-phase of the cell cycle [23] which could explain the increase in cell proliferation and therefore in tumor size.…”

“…It has been demonstrated that P 4 promotes astrocytomas growth [22–25] and that the administration of RU486 (PR antagonist) blocks P 4 effects [23, 26–28]. It has also been reported that RU486 improves the efficacy of chemoradiotherapy in glioblastoma xenografts in mice [29].…”

Mifepristone improves chemo-radiation response in glioblastoma xenografts

“…It is widely accepted that progesterone participates in the development of different types of cancer as a transcription factor [14,30,31]. It was reported [14,15] that progesterone-receptor isoforms are expressed in two cell lines (U373 and D54) derived from high-grade human astrocytoma. The same authors also demonstrated that progesterone increased VEGF and EGFR expression and cell proliferation, Mifepristone was able to inhibit not only the progesterone effects but also when it was administered alone significantly reduce astrocytoma cell growth in vitro.…”

“…The same authors also demonstrated that progesterone increased VEGF and EGFR expression, and cell proliferation in two human astrocytoma cell lines derived from tumors of different evolution grades (U373 grade III and D54 grade IV) and these effects were inhibited by Mifepristone [14,15]. Other authors have also showed that the expression of VEGF in prostate cancer cells DU 145 and PC3 treated with 10 micromol/L of Mifepristone was significantly decreased [16].…”