Progesterone (P4) participates in the regulation of several physiological and pathological processes in
mammals through the interaction with its intracellular receptors (PR), which are ligand-dependent transcription factors.
Many human cancers depend on P4 for growth and metastasis, especially cancers of reproductive tissues. In women,
administration of combined estrogen and progestin hormone replacement therapy for postmenopausal symptoms increases
the risk of breast cancer relative to women taking estrogens alone. P4 exerts its actions through various mechanisms
classified as classical and non-classical. PR has dual functions as a nuclear transcription factor and as a modulator of cell
signaling pathways. Many PR target genes do not contain canonical progesterone response elements (PRE) in their
promoter regions and may thus be regulated by PR tethering to other transcription factors and/or rapid signaling,
independent of direct PR DNA binding. We review the mechanisms involved in P4 effects on genes implicated in control
of cell cycle, proliferation, angiogenesis and metastasis, such as cyclin D1 and epidermal growth factor receptor (EGFR)
whose promoters lack PRE sequences, and vascular endothelial growth factor (VEGF) which gene contains PRE in its
promoter region. The understanding of the molecular mechanisms involved in the regulation of cyclin D1, EGFR and
VEGF expression by P4 will be helpful for the development of new cancer therapies.
Keywords: Cancer, Cyclin D1, Epidermal growth factor receptor, Progesterone, Progesterone receptor, Vascular endothelial, growth factor
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