Biomedical subjects

Haiyan Pan

Publications and source records attributed to Haiyan Pan.

4 recordsLinked to original sources

PubMed2006

Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing.

In the uterus, progesterone (P4) acts early in G1 as a physiological inhibitor of estradiol-17beta (E2)-induced epithelial cell proliferation. Gene expression profiling of uterine epithelial cell RNA isolated 3 h after hormonal treatment of ovariectomized mice revealed the co-coordinate down-regulation by P4 of >20 genes whose functions are associated with DNA replication. This group included all of the minichromosome maintenance (MCM) proteins that are required for DNA replication licensing. E2 regulated loading of these MCM proteins onto chromatin in parallel with its induction of DNA synthesis. E2 caused this chromatin loading by retention of MCM proteins in the nucleus and through the induction of the loading factor Cdt1, which is necessary for the MCM heterohexamer to bind to the origin of DNA replication. P4 dramatically reduced the binding of the MCMs to chromatin by a number of mechanisms. First, MCM mRNA and protein abundance was down-regulated. Second, P4 inhibited the E2 induction of Cdt1. Third, P4 treatment sequestered the normally nuclear MCM proteins into the cytoplasm. This reduced MCM binding resulted in the complete inhibition of E2-induced DNA synthesis by P4. These data reveal mechanisms not only for female sex steroid hormone action but also in the regulation of DNA replication licensing.

Animals↗

PubMed2006

Microarray analysis of uterine epithelial gene expression during the implantation window in the mouse.

In mice, the uterus becomes transiently receptive to the hatched blastocyst on the day of implantation to allow its attachment to the luminal epithelium and subsequent invasion into the uterus. This uterine preparation for implantation is regulated by estradiol-17beta and progesterone, acting through their transcription factor receptors. Using ovariectomized mice treated with physiological regimens of these hormones, combined with methods to isolate RNA specifically from the uterine epithelium followed by transcriptome analysis on cDNA microarrays, 222 genes whose transcript abundance was specifically increased by estradiol-17beta and progesterone treatment were identified. Gene ontology analysis revealed an emphasis on genes involved with immune responses, extracellular matrix metabolism, and cell-to-cell communication. In situ hybridization to uterine sections isolated through the first 6 d of pregnancy identified novel sets of genes such as Bach, Myd88, Cd14, Isg20, and Lrp2 whose expression was restricted to the uterine epithelium during the implantation window. Particularly notable was the expression of the mRNA for members of the signaling pathway from the Toll-like receptors to its downstream targets such as Irg-1. The identification of these genes showing a cell type hormonally regulated pattern of expression in the uterus suggests novel functions for them during implantation.

Animals↗

PubMed2005

Progesterone inhibits the estrogen-induced phosphoinositide 3-kinase-->AKT-->GSK-3beta-->cyclin D1-->pRB pathway to block uterine epithelial cell proliferation.

The mammalian cell cycle is regulated by the cyclin/cyclin-dependent kinase (CDK) phosphorylation of the retinoblastoma (pRB) family of proteins. Cyclin D1 with its CDK4/6 partners initiates the cell cycle and acts as the link between extracellular signals and the cell cycle machinery. Estradiol-17beta (E2) stimulates uterine epithelial cell proliferation, a process that is completely inhibited by pretreatment with progesterone (P4). Previously, we identified cyclin D1 localization as a key point of regulation in these cells with E2 causing its nuclear accumulation and P4 retaining it in the cytoplasm with the resultant inhibition of pRB phosphorylation. Here we show that E2 stimulates phosphoinositide 3-kinase to activate phosphokinase B/AKT to effect an inhibitory phosphorylation of glycogen synthase kinase (GSK-3beta). This pathway is suppressed by P4. Inhibition of the GSK-3beta activity in P4-treated uteri by the specific inhibitor, LiCl, reversed the nuclear accumulation of cyclin D1 and in doing so, caused pRB phosphorylation and the induction of downstream genes, proliferating cell nuclear antigen and Ki67. Conversely, inhibition of phosphoinositide 3 kinase by LY294002 or Wortmanin reversed the E2-induced GSK-3beta Ser9 inhibitory phosphorylation and blocked nuclear accumulation of cyclin D1. These data show the reciprocal actions of E2 and P4 on the phosphoinositide 3-kinase through to the GSK-3beta pathway that in turn regulates cyclin D1 localization and cell cycle progression. These data reveal a novel signaling pathway that links E2 and P4 action to growth factor-mediated signaling in the uterus.

Animals↗

PubMed2003

Genetic algorithms applied to multi-class clustering for gene expression data.

A hybrid GA (genetic algorithm)-based clustering (HGACLUS) schema, combining merits of the Simulated Annealing, was described for finding an optimal or near-optimal set of medoids. This schema maximized the clustering success by achieving internal cluster cohesion and external cluster isolation. The performance of HGACLUS and other methods was compared by using simulated data and open microarray gene-expression datasets. HGACLUS was generally found to be more accurate and robust than other methods discussed in this paper by the exact validation strategy and the explicit cluster number.

Algorithms↗