Expression of NANOG and NANOGP8 in a variety of undifferentiated and differentiated human cells.

The transcription factor NANOG is essential for maintaining pluripotency in embryonic stem cells. We have previously reported the expression of NANOG in adult human fibroblasts; here we present a more thorough investigation into the expression of NANOG in a panel of both differentiated and undifferentiated human cells. We utilize RT-PCR, qRT-PCR, cloning and sequencing, sequence alignment, restriction digestion, immunocytochemistry, Western blotting, and EMSA to investigate expression of NANOG in a variety of somatic, transformed and stem cell phenotypes.

Induction of stem cell gene expression in adult human fibroblasts without transgenes.

Reprogramming of differentiated somatic cells into induced pluripotent stem (iPS) cells has potential for derivation of patient-specific cells for therapy as well as for development of models with which to study disease progression. Derivation of iPS cells from human somatic cells has been achieved by viral transduction of human fibroblasts with early developmental genes. Because forced expression of these genes by viral transduction results in transgene integration with unknown and unpredictable potential mutagenic effects, identification of cell culture conditions that can induce endogenous expression of these genes is desirable.

CDK inhibitors selectively diminish cell cycle controlled activation of the histone H4 gene promoter by p220NPAT and HiNF-P.

Cell cycle progression into S phase requires the induction of histone gene expression to package newly synthesized DNA as chromatin. Cyclin E stimulation of CDK2 at the Restriction point late in G1 controls both histone gene expression by the p220(NPAT)/HiNF-P pathway and initiation of DNA replication through the pRB/E2F pathway. The three CDK inhibitors (CKIs) p21(CIP1/WAF1), p27(KIP1), and p57(KIP2) attenuate CDK2 activity.

Coordinate control and selective expression of the full complement of replication-dependent histone H4 genes in normal and cancer cells.

The replication of eukaryotic genomes necessitates the coordination of histone biosynthesis with DNA replication at the onset of S phase. The multiple histone H4 genes encode identical proteins, but their regulatory sequences differ. The contributions of these individual genes to histone H4 mRNA expression have not been described.

HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition.

Genome replication in eukaryotic cells necessitates the stringent coupling of histone biosynthesis with the onset of DNA replication at the G1/S phase transition. A fundamental question is the mechanism that links the restriction (R) point late in G1 with histone gene expression at the onset of S phase. Here we demonstrate that HiNF-P, a transcriptional regulator of replication-dependent histone H4 genes, interacts directly with p220(NPAT), a substrate of cyclin E/CDK2, to coactivate histone genes during S phase.

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines.

Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis.

Early events in the induction of apoptosis in ovarian carcinoma cells by CD437: activation of the p38 MAP kinase signal pathway.

Retinoids have great potential in the areas of cancer therapy and chemoprevention. 6-[3-(1-admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) is a conformationally restricted synthetic retinoid that has been reported to induce growth arrest and apoptosis in ovarian tumor cell lines but the entire mechanism for apoptotic induction has not been fully defined. We set out to identify the early events of CD437-induced apoptosis of the CA-OV-3 cell line and determine if these occur in a CA-OV-3 cell line resistant to CD437 (CA-CD437R).

Comparison of the mechanism of induction of apoptosis in ovarian carcinoma cells by the conformationally restricted synthetic retinoids CD437 and 4-HPR.

All-trans-retinoic acid (ATRA) has been shown to inhibit the growth of a number of ovarian tumor cell lines while others have been found to be resistant to retinoid suppression of growth. Interestingly, two synthetic retinoids, CD437 and 4-HPR, inhibit the growth of both ATRA-sensitive (CA-OV-3) and ATRA-resistant (SK-OV-3) ovarian tumor cells. However, in contrast to ATRA, both induce apoptosis.

Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents.

The polyphenolic compounds curcumin and quercetin increased sensitivity of ovarian cancer cells (CAOV3 and SKOV3) to cisplatin. The effect was obtained when the compounds were added simultaneously with cisplatin, as well as when they were added 24 h before. High serum levels of certain cytokines, for example interleukin-6 (IL-6), have been associated with poor prognosis and cisplatin resistance in various forms of cancer.

Elucidation of molecular events mediating induction of apoptosis by synthetic retinoids using a CD437-resistant ovarian carcinoma cell line.

Retinoids have great promise in the area of cancer therapy and chemoprevention. Although some tumor cells are sensitive to the growth inhibitory effect of all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-((1-Admantyl)-4-hydroxyphenyl)-2-naphthalenecarboxylic acid (CD437) is a conformationally restricted synthetic retinoid that induces growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines.