Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apoptosis cascade that plays a central role in normal and pathological processes is strictly controlled, in part by newly described members of the inhibitor of apoptosis (IAP) family (HIAP-1, HIAP-2, XIAP, NAIP, Survivin, and Livin). Here, we report the expression of IAP mRNAs and proteins in early and late gestation human placentas, term cytotrophoblast cells, and two choriocarcinoma cell lines, JEG-3 and Jar. Reverse transcriptase-polymerase chain reaction identified mRNAs derived from all of the currently known IAP genes in all samples. Analysis by immunoblotting revealed that IAP proteins are present in early and late gestation human placentas and that levels of IAPs are not identical in normal and transformed trophoblast cells. Immunohistochemical experiments performed on paraformaldehyde-fixed tissue sections taken from early and late stages of pregnancy demonstrated that expression patterns differed according to cell lineage and stage of cell differentiation. The results of this study are consistent with the postulate that IAP proteins have critical roles in placental cell survival and suggest that specific apoptosis inhibitors may protect normal and transformed trophoblast cells from cell death.
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PMID:Temporal and spatial patterns of expression of inhibitors of apoptosis in human placentas. 1287 63

Overexpression of the breast cancer resistance protein (BCRP/ABCG2) confers multidrug resistance (MDR) to tumor cells and often limits the efficacy of chemotherapy. To circumvent BCRP-mediated MDR, a common approach is the use of potent and specific inhibitors of BCRP transport such as fumitremorgin C, novobiocin, and GF120918. Here, we evaluated a new approach using RNA interference for the specific knockdown of BCRP. We designed and synthesized small interfering RNA (siRNA) using T7 RNA polymerase and showed that siRNAs markedly down-regulated both exogenous and endogenous expression of BCRP. As a functional consequence, knockdown of BCRP by siRNAs increased the sensitivity of human choriocarcinoma BeWo cells to mitoxantrone and topotecan by 10.5- and 8.2-fold, respectively. Using flow cytometry, we found that introduction of siRNAs also enhanced the intracellular accumulation of topotecan. We have previously identified an estrogen response element in the BCRP promoter and have shown that 17beta-estradiol increased BCRP mRNA expression. Furthermore, in the present study, we found that expression of BCRP protein was inducible by 17beta-estradiol and that this effect was ameliorated by the introduction of siRNAs. These studies indicate that siRNAs could modulate MDR in vitro and may present a new approach to overcome BCRP-mediated drug resistance.
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PMID:Modulation of breast cancer resistance protein (BCRP/ABCG2) gene expression using RNA interference. 1563 51

The apoptosis cascade that plays a central role in normal and pathological processes is strictly controlled, in part by FLIP (Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein), an inhibitor of caspase-8. Here, we report the expression of long and short isoforms of FLIP mRNAs and proteins in early and late gestation human placentas, term cytotrophoblast cells and two choriocarcinoma cell lines, JEG-3 and Jar. Reverse transcriptase polymerase chain reaction identified mRNAs derived from the FLIP gene in all samples. Analysis by immunoblotting revealed that both long and short forms of FLIP proteins are present in early and late gestation human placentas with increasing levels over gestation and that FLIP proteins are present in normal and transformed trophoblast cells. Immunohistochemical experiments performed on paraformaldehyde-fixed tissue sections taken from early and late stages of pregnancy demonstrated that FLIP proteins are present in caspase-8-expressing cells and that expression patterns of FLIP differed according to cell lineage and stage of cell differentiation. The results of this study are consistent with the postulate that FLIP proteins have critical roles in placental cell survival and suggest that FLIP may protect normal and transformed trophoblast cells from cell death.
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PMID:FLICE-inhibitory protein: expression in early and late gestation human placentas. 1617 30

Our previous findings showed that galectin-1 (LGALS1) plays an important role in the in vitro invasion of normal human trophoblast cells. In the present study, choriocarcinoma JAr cells were found to express LGALS1, -2, -3, -8, -10, and -13 mRNA and at least LGALS1, -3, and -8 protein, as determined by reverse-transcriptase PCR and Western blot, respectively. The galectin mRNA signature of JAr cells thus differed from that of normal first-trimester extravillous trophoblasts. A Matrigel migration assay was also used to investigate and confirm the relevance and effect of LGALS1 on the invasive potential of JAr cells, as observed in other trophoblast models. This modulation in behavior was achieved by specific lectin-glycan binding.
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PMID:Galectin signature of the choriocarcinoma JAr cells: Galectin-1 as a modulator of invasiveness in vitro. 2609 42


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