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Xiao-Fei Ding Jun Zhou Qiong-Ying Hu Shuang-Chun Liu Guang Chen 《The Journal of biological chemistry》2015,290(3):1389-1394
NEK8 (never in mitosis gene A (NIMA)-related kinase 8) is involved in cytoskeleton, cilia, and DNA damage response/repair. Abnormal expression and/or dysfunction of NEK8 are related to cancer development and progression. However, the mechanisms that regulate NEK8 are not well declared. We demonstrated here that pVHL may be involved in regulating NEK8. We found that CAK-I cells with wild-type vhl expressed a lower level of NEK8 than the cells loss of vhl, such as 786-O, 769-P, and A-498 cells. Moreover, pVHL overexpression down-regulated the NEK8 protein in 786-O cells, whereas pVHL knockdown up-regulated NEK8 in CAK-I cells. In addition, we found that the positive hypoxia response elements (HREs) are located in the promoter of the nek8 sequence and hypoxia could induce nek8 expression in different cell types. Consistent with this, down-regulation of hypoxia-inducible factors α (HIF-1α or HIF-2α) by isoform-specific siRNA reduced the ability of hypoxia inducing nek8 expression. In vivo, NEK8 and HIF-1α expression were increased in kidneys of rats subjected to an experimental hypoxia model of ischemia and reperfusion. Furthermore, NEK8 siRNA transfection significantly blocked pVHL-knockdown-induced cilia disassembling, through impairing the pVHL-knockdown-up-regulated NEK8 expression. These results support that nek8 may be a novel hypoxia-inducible gene. In conclusion, our findings show that nek8 may be a new HIF target gene and pVHL can down-regulate NEK8 via HIFs to maintain the primary cilia structure in human renal cancer cells. 相似文献
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Summary This paper describes the ovarian pathologies observed when 108 different heteroallelic combinations were made involving 17 independent mutations at the ovarian tumor (otu) locus. Most of the mutant phenotypes can be explained as graded responses by individual germ cells to different levels of functionally active otu gene product (OGP) synthesized by the mutant cells themselves. The lowest and highest levels of OGP appear to be produced by otu
10 and otu
14, respectively. In most heteroallelic ovaries the alleles have additive effects, and hybrid germ cells reach a developmental stage more advanced than the weaker homozygote but less advanced than the stronger homozygote. However, examples of both positive and negative complementation also have been found, and these suggest that the products encoded by different mutant alleles can combine to form dimers or multimers which may be superior or inferior to the homodimers. In flies homozygous for otu
11 most ovarioles contain tumors, but some germ cells are able to develop further than those in otu
14 homozygotes. This suggests that, while otu
11 produces intermediate levels of OGP, it also produces a second product (which otu
14 cannot make) that is utilized at the period in oogenesis when development in cells homozygous for otu
14 is blocked. When otu
11 is combined with any one of eight specific alleles, it allows oocyte/nurse cell syncytia to differentiate that can complete development and undergo embryogenesis, if fertilized. The endopolyploid nurse cells of these hybrids have giant polytene chromosomes, and the presence of GPCs in functionally active, germ-line derived cells provides an interesting new system for experimental study. Analysis of the characteristic ovarian pathologies produced by flies of different genotypes leads to the conclusion that the products of the otu
+ gene are utilized during at least six different periods in Drosophila oogenesis. 相似文献
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Giuseppe Familiari M.D. Stefania A. Nottola Antonio Familiari Pietro M. Motta 《Cell and tissue research》1989,257(2):247-253
Summary The present study provides further details on the fine-structural three-dimensional architecture of the zona pellucida (ZP) in growing and atretic follicles of mice by use of ruthenium red in combination with the detergents Triton X100 and saponin. These detergents were used for extraction of the soluble fraction of the zonal proteins in an attempt to expose the structural zonal glycoproteins, which in turn can be viewed as minute three-dimensional networks upon transmission- and scanning electron-microscopic examination. By use of these methods, the ZP of growing follicles appeared to be formed by interconnected filaments which also bind to globular structures building up a three-dimensional lattice. In contrast, the ZP of stage I as well as other (II and III) stages of atretic follicles showed a structure characterized by the presence of closely packed granules connected with short filaments to form a close-mesh reticulum. This structural change of the ZP, which in the present study is also associated with the disappearance of gap junctions within the granulosa and cumulus cell population, might represent one of the early events involved in the onset of atresia. These changes, most probably depending on an altered secretory activity of both oocytes and follicle cells, might lead to a degradation of the ZP network structure and to its subsequent increased density (condensation). All these morphodynamic events eventually contribute to a sequestration of the oocyte in the early stage of atresia. 相似文献
6.
M. Apiranthitou-Drogari C. Paganin S. Bernasconi G. Losa A. Maneo N. Colombo A. Mantovani P. Allavena 《Cancer immunology, immunotherapy : CII》1992,35(4):289-295
Summary Lymphocytes infiltrating human ovarian carcinoma obtained directly from the tumour mass (tumour-infiltrating lymphocytes, TIL) or from the carcinomatous ascites (tumour-associated lymphocytes, TAL) were expanded in vitro in long-term cultures with interleukin-2 and tested for their specific cytolytic activity. Killing of the autologous tumour was detected only in a proportion of the patients, less frequently in TIL compared to TAL. In fact two out of ten TIL and four out of nine TAL cultures tested showed significant levels of lysis against the autologous tumour. This cytotoxic activity was not restricted to the autologous tumour, as other tumour cell lines, including non-ovarian ones, were lysed as well. The cultures that were not cytotoxic against the autologous tumour were in most cases able to lyse other tumour cell lines of ovarian or other histology. Cloning of TIL from one patient was performed: of 22 clones tested, 4 displayed higher cytotoxicity against the autologous tumour compared to the uncloned population and 3 out of these 4 did not kill an irrelevant carcinoma cell line. In order to stimulate the expansion of putative specific effectors we performed mixed lymphocyte/tumour cultures (MLTC) with autologous or allogeneic tumour cells. No stimulation of cytotoxicity against the autologous tumour was detected after MLTC in nine different TAL populations, using autologous or allogeneic tumours as stimulators. On the contrary, peripheral blood lymphocytes from two patients after MLTC with the autologous tumour showed increased killing of the autologous and decreased killing of an allogeneic target. In conclusion TIL and TAL from ovarian carcinoma expanded in vitro with interleukin-2 usually have non-MHC-restricted cytotoxicity and variable degrees of reactivity against the autologous tumour. A preferential killing for the autologous tumour was not observed even after MLTC. These results do not exclude the existence of tumour-specific cytotoxic T lymphocytes in ovarian carcinoma; nevertheless they suggest that putative specific effectors have very low frequency and that culture techniques for expanding their growth more selectively are still to be optimized. 相似文献
7.
本文为探讨硒抗肿瘤的机理而开展了硒对小鼠腹水型肝癌(Hep.A)细胞膜流动性影响的研究。结果表明;1.腹水型肝癌细胞膜流动性明显高于正常肝细胞的膜流动性。2.硒能显著降低腹水型肝癌细胞膜的流动性,而对正常肝细胞的膜流动性没有明显影响。3.通过降低腹水型肝癌细胞膜的流动性,可降低肿瘤细胞的致癌力。 相似文献
8.
Summary The changes in ovarian activity in the life cycle of the eusocial halictine beeLasioglossum (Evylaeus) duplex (Dalla Torre) was studied in both queens and workers by examining the stages of the terminal follicle in each of the six ovarioles. By
this method, ovarian activities of both queens and workers were more quantitatively determined than by observation of gross
ovarian features as usually conducted. Queen ovaries clearly exhibited two active periods, corresponding to the spring solitary
phase and the summer eusocial phase, with distinctly greater activity in the latter. In ovaries of overwintering queens oosorption
of young follicle was observed. Worker ovaries were found more active in orphan than in queenright colonies. The order of
ovarian activity obtained from pooled data, summer queens>spring queens>orphan workers>queenright workers, was also recognized
by comparison of individual females.
Bionomics of the eusocial halictine beeLasioglossum duplex IX.
Contribution No. 3107 from the Inst. Low Temp. Sci. 相似文献
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本文报告一种为适于杂交瘤细胞生长“无血清”培养基-适量的成牛血清低分子成分超滤液、10mg/L转铁蛋白(T)、10mg/L胰岛素(I)、20μmol/L乙醇胺(E)、40nmol/L硒酸钠(S)等诸补充成分替代胎牛血清加到基础液中-也完全适用于培养肿瘤细胞,且观察到与之相似的规律性结果,癌细胞在本“无血清”培养若的生长水平达到在含胎牛血清培养基中生长的水平。对于癌细胞的生长,LMW-CS与T、I、 相似文献