TY  - JOUR
A1  - Hammes, Annette
A1  - Andreassen, Thomas K.
A1  - Spoelgen, Robert
A1  - Raila, Jens
A1  - Hubner, Norbert
A1  - Schulz, Herbert
A1  - Metzger, Jochen
A1  - Schweigert, Florian J.
A1  - Luppa, Peter B.
A1  - Nykjaer, Andreas
A1  - Willnow, Thomas E.
T1  - Role of endocytosis in cellular uptake of sex steroids
N2  - Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs
Y1  - 2005
SN  - 0092-8674
ER  - 
TY  - JOUR
A1  - Schlag, Peter M.
A1  - Osterziel, Karl Joseph
A1  - Özcelik, Cemil
A1  - Scherneck, Siegfried
A1  - Wenzel, Katrin
A1  - Daskalow, Katjana
A1  - Herse, Florian
A1  - Seitz, Susanne
A1  - Zacharias, Ute
A1  - Schenk, Jörg A.
A1  - Schulz, Herbert
A1  - Hübner, Norbert
A1  - Micheel, Burkhard
T1  - The protein phosphatase 1 inhibitor KEPI is down regulated in breast cancer cell lines and tissues and involved in the regulation of the tumour suppressor EGR1 via the MEK-ERK pathway
N2  - KEPI is a protein kinase C-potentiated inhibitory protein for type 1 Ser/Thr protein phosphatases. We found no or reduced expression of KEPI in breast cancer cell lines, breast tumors and metastases in comparison to normal breast cell lines and tissues, respectively. KEPI protein expression and ubiquitous localization was detected with a newly generated antibody. Ectopic KEPI expression in MCF7 breast cancer cells induced differential expression of 95 genes, including the up-regulation of the tumor suppressors EGR1 (early growth response 1) and PTEN (phosphatase and tensin homolog), which is regulated by EGR1. We further show that the up-regulation of EGR1 in MCF7/KEPI cells is mediated by MEK-ERK signaling. The inhibition of this pathway by the MEK inhibitor UO126 led to a strong decrease in EGR1 expression in MCF7/KEPI cells. These results reveal a novel role for KEPI in the regulation of the tumor suppressor gene EGR1 via activation of the MEK-ERK MAPK pathway.
Y1  - 2008
UR  - http://www.atypon-link.com/doi/abs/10.1515/BC.2007.062
ER  -