Dataset Information

The tumor suppressor p53 induces expression of the pregnancy-supporting human chorionic gonadotropin (hCG) CGB7 gene.

ABSTRACT: Successful pregnancy requires a functionally normal blastocyst encountering a receptive maternal endometrium. Interestingly, the cell cycle regulator and tumor suppressor p53 has been reported to support reproduction in mice by regulating the expression of the leukemia inhibitory factor gene in the maternal endometrium. However, in humans the hormonal system orchestrating successful pregnancy is considerably different from rodents. Particularly, the primate-specific dimeric glycoprotein hormone human chorionic gonadotropin (hCG) is essential for blastocyst implantation and maintenance of early human pregnancy. Here we provide evidence that p53 selectively induces expression of the hCGbeta7 (CGB7) gene. None of the other CGB genes was found to be regulated by p53. We show that expression of the CGB7 gene is upregulated upon p53 induction in human HFF, HCT116 and DLD1 cells as well as in cell preparations enriched in human primary first-trimester trophoblasts. The increase in CGB7 levels upon doxorubicin treatment is lost after siRNA-directed knockdown of p53. Furthermore, we describe CGB7 as a direct transcriptional target gene of p53 by identifying a p53-responsive element in the CGB7 promoter using reporter assays, electrophoretic mobility shift assays and chromatin immunoprecipitations. With these results we provide a new link between p53 transcriptional activity and human reproduction.

SUBMITTER: Sohr S

PROVIDER: S-EPMC3266010 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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The tumor suppressor p53 induces expression of the pregnancy-supporting human chorionic gonadotropin (hCG) CGB7 gene.

Sohr Sindy S Engeland Kurt K

Cell cycle (Georgetown, Tex.) 20111101 21

Successful pregnancy requires a functionally normal blastocyst encountering a receptive maternal endometrium. Interestingly, the cell cycle regulator and tumor suppressor p53 has been reported to support reproduction in mice by regulating the expression of the leukemia inhibitory factor gene in the maternal endometrium. However, in humans the hormonal system orchestrating successful pregnancy is considerably different from rodents. Particularly, the primate-specific dimeric glycoprotein hormone ...[more]

PMID: 22032922

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Project description:BackgroundA positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation. Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy.MethodsHuman chorionic gonadotropin was examined in female dialysis patients (18-50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu's method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression.ResultsAmong 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin.ConclusionHuman chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.

Dataset Information

The tumor suppressor p53 induces expression of the pregnancy-supporting human chorionic gonadotropin (hCG) CGB7 gene.

Publications

The tumor suppressor p53 induces expression of the pregnancy-supporting human chorionic gonadotropin (hCG) CGB7 gene.

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