Expression of estrogen receptor coregulators in normal and malignant human endometrium.
OBJECTIVE
To compare the expression of nuclear receptor coregulators in normal and malignant human endometrium and to identify any relationship to grade, stage, age, depth of myometrial invasion, estrogen receptor alpha (ERalpha), or progesterone receptor (PR) expression.


METHODS
Gene expression of SRC-1, SRC-2, SRC-3, N-CoR, SMRT, ERalpha, and PR was measured in 26 samples of normal endometrium and 30 primary endometrial carcinomas using real-time RT-PCR. ERalpha protein expression of each tissue was also measured by Western blot.


RESULTS
. All coregulators showed significantly increased mRNA expression in endometrial carcinoma as compared to normal endometrium. The mRNA expression of each coregulator showed a high correlation with ERalpha mRNA, PR mRNA, and with the other coregulators in both normal and malignant endometrium. In the normal endometrium, SRC-1 mRNA expression was positively correlated with ERalpha protein expression and SRC-3 mRNA expression was positively correlated with patient age. No relationship was found between coregulator mRNA expression and grade, stage, or depth of myometrial invasion.


CONCLUSIONS
The nuclear receptor coregulators SRC-1, SRC-2, SRC-3, N-CoR, and SMRT were found to be up-regulated in malignant endometrium. Our findings suggest that these proteins may have a role in the development of endometrial carcinoma.
Kershah
Sharif M
SM
Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo, OH 43614, USA.
Desouki
Mohamed Mokhtar
MM
Koterba
Kristen L
KL
Rowan
Brian G
BG
D000123:Acetyltransferases; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000502:physiology; D047628:Estrogen Receptor alpha; D005260:Female; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538866:NCOA3 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3