TY - JOUR
T1 - Regulation of PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10) Expression by Estradiol and Progesterone in Human Endometrium
AU - Guzeloglu-Kayisli, Ozlem
AU - Kayisli, Umit A.
AU - Al-Rejjal, Rafat
AU - Zheng, Wenxin
AU - Luleci, Guven
AU - Arici, Aydin
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/10
Y1 - 2003/10
N2 - PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor gene, mutated frequently in a variety of human tumors. PTEN regulates cell growth, apoptosis, and proliferation. Phosphorylation in PTEN tail causes its inactivation and decreases its degradation. There is little known about the regulation of PTEN by ovarian steroids. We hypothesized that PTEN expression in human endometrium is variable throughout the menstrual cycle and early pregnancy, and that ovarian steroids regulate PTEN expression because PTEN is critical in many steroid-sensitive tissues such as endometrium, prostate, and breast. In the present study, we have observed a direct regulation of PTEN by ovarian steroids. Estradiol increased PTEN phosphorylation at 5-15 min. After 24-h treatment, progesterone induced a significant increase in PTEN protein levels, assessed by Western blot. Furthermore, we evaluated for the first time a comparison between menstrual cycle and early pregnancy, immunohistochemically. Endometrial PTEN expression revealed temporal and spatial changes throughout the menstrual cycle and during early pregnancy. We conclude that estradiol may down-regulate PTEN activity by increasing its phosphorylation, but progesterone is likely to regulate the PTEN pool by decreasing its phosphorylation and increasing its protein level. Presented data, therefore, suggest that ovarian steroids regulate the endometrial PTEN pool. We propose that PTEN might be one of the signaling proteins that estrogen and progesterone are acting to affect endometrial cell proliferation and/or apoptosis.
AB - PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor gene, mutated frequently in a variety of human tumors. PTEN regulates cell growth, apoptosis, and proliferation. Phosphorylation in PTEN tail causes its inactivation and decreases its degradation. There is little known about the regulation of PTEN by ovarian steroids. We hypothesized that PTEN expression in human endometrium is variable throughout the menstrual cycle and early pregnancy, and that ovarian steroids regulate PTEN expression because PTEN is critical in many steroid-sensitive tissues such as endometrium, prostate, and breast. In the present study, we have observed a direct regulation of PTEN by ovarian steroids. Estradiol increased PTEN phosphorylation at 5-15 min. After 24-h treatment, progesterone induced a significant increase in PTEN protein levels, assessed by Western blot. Furthermore, we evaluated for the first time a comparison between menstrual cycle and early pregnancy, immunohistochemically. Endometrial PTEN expression revealed temporal and spatial changes throughout the menstrual cycle and during early pregnancy. We conclude that estradiol may down-regulate PTEN activity by increasing its phosphorylation, but progesterone is likely to regulate the PTEN pool by decreasing its phosphorylation and increasing its protein level. Presented data, therefore, suggest that ovarian steroids regulate the endometrial PTEN pool. We propose that PTEN might be one of the signaling proteins that estrogen and progesterone are acting to affect endometrial cell proliferation and/or apoptosis.
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U2 - 10.1210/jc.2003-030414
DO - 10.1210/jc.2003-030414
M3 - Article
C2 - 14557489
AN - SCOPUS:0242288646
SN - 0021-972X
VL - 88
SP - 5017
EP - 5026
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -