Steroid receptor coactivator 2: an essential coregulator of progestin-induced uterine and mammary morphogenesis.
The importance of the progesterone receptor (PR) in transducing the progestin signal is firmly established in female reproductive and mammary gland biology; however, the coregulators preferentially recruited by PR in these systems have yet to be comprehensively investigated. Using an innovative genetic approach, which ablates gene function specifically in murine cell-lineages that express PR, steroid receptor coactivator 2 (SRC-2, also known as TIF-2 or GRIP-1) was shown to exert potent coregulator properties in progestin-dependent responses in the uterus and mammary gland. Uterine cells positive for PR (but devoid of SRC-2) led to an early block in embryo implantation, a phenotype not shared by knockouts for SRC-1 or SRC-3. In the case of the mammary gland, progestin-dependent branching morphogenesis and alveologenesis failed to occur in the absence of SRC-2, thereby establishing a critical coactivator role for SRC-2 in cellular proliferative programs initiated by progestins in this tissue. Importantly, the recent detection of SRC-2 in both human endometrium and breast suggests that this coregulator may provide a new clinical target for the future management of female reproductive health and/or breast cancer.
Mukherjee
A
A
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, 77030 Houston, USA.
Amato
P
P
Craig-Allred
D
D
DeMayo
F J
FJ
O'Malley
B W
BW
Lydon
J P
JP
D000818:Animals; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000254:growth & development*; D009024:Morphogenesis; D051958:Nuclear Receptor Coactivator 2 / Q000502:physiology*; D011372:Progestins / Q000502:physiology*; D014599:Uterus / Q000254:growth & development*
D051958:Nuclear Receptor Coactivator 2; D011372:Progestins