Impact of Progesterone on Stem/Progenitor Cells in the Human Breast

Abstract

The epithelium of the human breast is made up of a branching ductal-lobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormone, progesterone, is critical in driving proliferation and normal breast development, yet progesterone analogues have also been shown to be a major driver of breast cancer risk. Studies in recent years have revealed an important role for progesterone in stimulating the mammary stem cell compartment in the mouse mammary gland, and growing evidence supports the notion that progesterone also stimulates progenitor cells in both the normal human breast and in breast cancer cells. As changes in cell type composition are one of the hallmark features of breast cancer progression, these observations have critical implications in discerning the mechanisms of how progesterone increases breast cancer risk. This review summarises recent work regarding the impact of progesterone action on the stem/progenitor cell compartment of the human breast.

Fetal Estetrol (E4) Inhibits Growth Hormone (GH) Signal Transduction in Breast Cancer Cell Lines

“…For estrogens, this will only work in those cells that co-express both GHR and ER. So far, no expression of ER has been shown in mammary stem cells, but in luminal progenitor cells the highest copy numbers of ER are found relative to unsorted cells or fully differentiated cells [34], and may therefore present cells that can be sensitive to GHR inhibition by estrogens. There is an ongoing discussion on the role of estrogens in female reproductive cancers [35,36].…”

Hormone Therapy and Risk of Breast Cancer: Where Are We Now?

“…Estradiol heightens the risk of breast cancer in postmenopausal women and preclinical studies have demonstrated that progestin engenders progenitor cells in both human and breast cancer cells [ 11 12 13 ]. While estrogen and progesterone levels significantly decline following menopause, HRT-induced blood estrogen levels correlate with an increased incidence of estrogen receptor-positive breast cancer, especially in women with a higher body mass index [ 13 ].…”

Modern understanding of risk factors and mechanisms of breast cancer development

“…В связи с этим целесообразно рассмотреть значимые звенья патогенеза РМЖ, условно разделив их на несколько этиопатогенетических групп. Очевидным значимым фактором риска развития РМЖ является женский пол [9]. Данное обстоятельство определяет начальные этапы канцерогенеза, ключевым образом зависящие от действия эстрогенов (ERs) и прогестерона (PG) [3,10].…”