• 【睾丸生殖细胞瘤过度表达野生型p53。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Guillou L,Estreicher A,Chaubert P,Hurlimann J,Kurt AM,Metthez G,Iggo R,Gray AC,Jichlinski P,Leisinger HJ,Benhattar J
    BACKGROUND & AIMS: Several recent studies have suggested that testicular germ cell tumors express high levels of wild-type p53 protein. To clarify and confirm this unexpected result, we have investigated seminomatous and nonseminomatous germ cell tumors at the genomic, mRNA, and protein levels. Thirty-five tumors were examined for p53 overexpression using antibodies directed against the p53 (PAb1801, PAb240, and CM1), mdm2 (IF2), and p21Waf1/Clp1 (EA10) proteins. Thirty-two tumors were screened for p53 mutations by single-strand conformation polymorphism analysis. Eighteen tumors were screened with a functional assay that tests the transcriptional competence of human p53 protein expressed in yeast. On frozen sections, 100, 65, 35, 73, and 0% of tumors reacted with the CM1, PAb240, PAb1801, IF2, and EA10 antibodies, respectively. No p53 mutations were detected by single-strand conformation polymorphism or by functional assay. The fact that many tumors overexpress wild-type p53 but not mdm2 rules out mdm2 overexpression as a general explanation for the presence of wild-type p53 in these tumors. The absence of p21 overexpression suggests that p53 may be unable to activate transcription of critical target genes, which may explain why the presence of wild-type p53 is tolerated in this tumor type, although the mechanism for this transcriptional inactivity remains to be established.

    背景与目标: 最近的一些研究表明,睾丸生殖细胞肿瘤表达高水平的野生型p53蛋白。为了澄清和确认这一意外结果,我们在基因组,mRNA和蛋白质水平上研究了精原细胞和非精原细胞生殖细胞肿瘤。使用针对p53 (PAb1801,PAb240和CM1),mdm2 (IF2) 和p21Waf1/Clp1 (EA10) 蛋白的抗体检查了35个肿瘤的p53过表达。通过单链构象多态性分析筛选了32个肿瘤的p53突变。用功能测定法筛选了18个肿瘤,该测定法测试了酵母中表达的人p53蛋白的转录能力。在冷冻切片上,100、65、35、73和0% 的肿瘤分别与CM1、PAb240、PAb1801、IF2和EA10抗体反应。通过单链构象多态性或功能分析未检测到p53突变。许多肿瘤过表达野生型p53而非mdm2的事实排除了mdm2过表达作为这些肿瘤中野生型p53存在的一般解释。p21过表达的缺乏表明p53可能无法激活关键靶基因的转录,这可以解释为什么在这种肿瘤类型中可以耐受野生型p53的存在,尽管这种转录不活跃的机制仍有待建立。
  • 【一氧化氮对青春期前单侧睾丸扭转大鼠对侧睾丸的保护作用。】 复制标题 收藏 收藏
    DOI:10.1046/j.1464-410x.2000.00529.x 复制DOI
    作者列表:Dokucu AI,Oztürk H,Ozdemir E,Ketani A,Büyükbayram H,Yücesan S
    BACKGROUND & AIMS: OBJECTIVE:To investigate histological changes in the contralateral testis of rats with unilateral testicular torsion and the protective effects of nitric oxide (NO) on possible damage. MATERIAL AND METHODS:Twenty-eight prepubertal male Sprague-Dawley rats were divided into four equal groups. Group 1 underwent a sham operation of the right testis under general anaesthesia. Group 2 underwent a similar operation but the right testis was rotated 720 degrees clockwise for 6 h, maintained by fixing the testis to the scrotum, and saline infused during the procedure. Group 3 underwent similar torsion but L-arginine methyl ester (a precursor of NO) was infused during the procedure. In Group 4, NG-nitro-L-arginine-methyl ester, a NO synthase inhibitor, was infused separately during the administration of L-arginine methyl ester and torsion. All the left (untwisted) testes were removed from rats 21 days after surgery and evaluated histologically, assessing seminiferous tubule diameter, loss of sperm and spermatids, loss of germ cell layers, disarray of germ cell layers, rupture of tubules, Leydig cell proliferation and reaction in the ruptured tubules, and oedema. RESULTS:There was a significant difference in the indicators of histological damage between groups 2 and 4 and groups 1 and 3, except for the Leydig cell reaction in the ruptured tubules and oedema. The damage was significantly less in group 3 than in groups 2 and 4. CONCLUSION:These results suggest that long-term histopathological changes in the contralateral testes are important after unilateral testicular torsion and that NO has a protective effect on the contralateral testis.
    背景与目标:
  • 【发育中的小鼠睾丸生殖细胞和支持细胞中DNA甲基化模式的改变。】 复制标题 收藏 收藏
    DOI:10.1159/000015460 复制DOI
    作者列表:Coffigny H,Bourgeois C,Ricoul M,Bernardino J,Vilain A,Niveleau A,Malfoy B,Dutrillaux B
    BACKGROUND & AIMS: :In situ alterations of DNA methylation were studied between 14 d postcoitum and 4 d postpartum in Sertoli cells and germ cells from mouse testis, using anti-5-methylcytosine antibodies. Compared to cultured fibroblasts, Sertoli cells display strongly methylated juxtacentromeric heterochromatin, but hypomethylated chromatids. Germ cells always possess hypomethylated heterochromatin, whereas their euchromatin passes from a demethylated to a strongly methylated status between days 16 and 17 postcoitum. This hypermethylation occurs in the absence of DNA replication, germ cells being blocked in the G(0)-G(1) phase from day 15 postcoitum to birth. The DNA hypermethylation of germ cells is maintained until birth and could be visualized on both chromatids of metaphase chromosomes at the first postpartum cell division. Subsequently, the DNA hypermethylation is lost semiconservatively, being replaced by a methylation pattern recalling the typical fibroblast pattern. These alterations of DNA methylation follow a strict chronology, are chromosome structure and cell-type dependent, and may underlie profound changes of genome function.
    背景与目标: : 使用anti-5-methylcytosine抗体研究了小鼠睾丸支持细胞和生殖细胞在产后14 d和产后4 d之间DNA甲基化的原位改变。与培养的成纤维细胞相比,Sertoli细胞显示出强烈的甲基化的间生异染色质,但低甲基化的染色单体。生殖细胞始终具有低甲基化的异染色质,而它们的常染色质在第16至17天之间从去甲基化状态转移到强烈甲基化状态。这种高甲基化发生在没有DNA复制的情况下,生殖细胞从出生后第15天到出生在G(0)-G(1) 阶段被阻断。生殖细胞的DNA高甲基化一直维持到出生,并且可以在产后第一次细胞分裂时在中期染色体的两个染色单体上观察到。随后,DNA超甲基化被半保守地丢失,被甲基化模式取代,使其回想起典型的成纤维细胞模式。DNA甲基化的这些改变遵循严格的时间顺序,是染色体结构和细胞类型依赖性的,并且可能是基因组功能深刻变化的基础。
  • 【睾丸原发性大细胞非霍奇金淋巴瘤: 失败模式和预后因素的回顾性分析。】 复制标题 收藏 收藏
    DOI:10.3816/clm.2001.n.016 复制DOI
    作者列表:Seymour JF,Solomon B,Wolf MM,Janusczewicz EH,Wirth A,Prince HM
    BACKGROUND & AIMS: :We have analyzed 25 patients with primary testicular large-cell non-Hodgkin's lymphoma managed at our institution from 1972-1998. The median age was 69 years, with bilateral testicular involvement in 16%. The disease stage was I in 56%, II in 32%, and IV in 12%. Twenty-four patients received further therapy after orchiectomy, including chemotherapy in 18 and radiation therapy in 11 (encompassing regional nodes in 8 and the contralateral testis in 6), with 5 patients receiving both modalities. The complete remission rate was 88%, but a continuous pattern of recurrence is evident up to 10 years, when only 23% of patients are predicted to be in ongoing remission. The dominant sites of first failure were extranodal (91%), with prominent involvement of the contralateral testis and cerebral parenchyma. The 10-year overall survival rate is 32%, and the median overall survival is 4.4 years. Within the entire cohort, adverse prognostic factors for treatment failure were serum albumin < or = to 3.5 g/dL (P = 0.02), advanced age, advanced stage, and lack of anthracycline-containing chemotherapy (each P < or = to 0.3). Among patients with locoregional disease, albumin < or = to 3.5 g/dL (P = 0.08), no anthracycline-containing chemotherapy (P = 0.15), and fewer than 6 cycles of chemotherapy (P = 0.03) remained predictive. Based on this analysis, we are prospectively evaluating a treatment program for patients with testicular non-Hodgkin's large-cell lymphoma comprising (1) 6 cycles of anthracycline-based chemotherapy, (2) prophylactic radiation therapy to the contralateral testis, and (3) central nervous system prophylaxis with both intrathecal chemotherapy and systemic high-dose methotrexate.
    背景与目标: : 我们分析了1972-1998年在我们机构管理的25例原发性睾丸大细胞非霍奇金淋巴瘤患者。中位年龄69岁,16% 双侧睾丸受累。疾病阶段为56% 年I,32% 年II,12% 年IV。24例患者在睾丸切除术后接受了进一步的治疗,包括18例化疗和11例放疗 (包括8例区域淋巴结和6例对侧睾丸),其中5例接受了两种方式。完全缓解率是88% 的,但是当预测只有23% 的患者处于持续缓解期时,持续10年的复发模式是明显的。首次失败的主要部位是结外 (91%),对侧睾丸和脑实质明显受累。10年总生存率为32%,中位总生存率为4.4年。在整个队列中,治疗失败的不良预后因素是血清白蛋白 <或 = 3.5g/dL (P = 0.02),高龄,晚期和缺乏含蒽环类药物的化疗 (每个P <或 = 0.3)。在局部区域疾病患者中,白蛋白 <或 = 3.5g/dL (P = 0.08),没有含蒽环类药物的化疗 (P = 0.15) 和少于6个周期的化疗 (P = 0.03) 仍然是可预测的。基于此分析,我们正在前瞻性评估睾丸非霍奇金大细胞淋巴瘤患者的治疗计划,包括 (1) 6个周期的基于蒽环类药物的化疗,(2) 对侧睾丸的预防性放射治疗,(3) 鞘内化疗和全身大剂量甲氨蝶呤预防中枢神经系统。
  • 【睾丸未降和睾丸癌的风险: 暴露信息来源和分类的重要性。】 复制标题 收藏 收藏
    DOI:10.1093/ije/30.5.1050 复制DOI
    作者列表:Stang A,Ahrens W,Bromen K,Baumgardt-Elms C,Jahn I,Stegmaier C,Krege S,Jöckel KH
    BACKGROUND & AIMS: BACKGROUND:The strength of the association between undescended testis and testicular cancer varies considerably across studies. Here we report the effect of various classifications of self-reported history of undescended testis and different data sources on the estimates of the risk of testicular cancer from a case-control study. METHODS:We performed a population-based case-control study including 269 testicular cancer cases and 797 controls matched on age and region. Medical history was assessed by interviews (index persons) and mailed questionnaires (mothers). We used conditional logistic regression to calculate odds ratios (OR) and kappa coefficients to assess agreement between different sources of information. RESULTS:Odds ratios for testicular cancer ranged between 2.4 and 5.4 based on the sons' self-reports and between 1.1 and 1.9 based on the mothers' reports. The agreement between the sons and mothers on undescended, gliding or retractile testis was fair (kappa 0.53) and was good when these conditions were treated by surgery (kappa 0.89). The rating of a history of undescended testis by two urologists was fair (kappa 0.54). CONCLUSIONS:The questionnaire design, the classifications of undescended testis and data sources have an important impact on the OR for the association of undescended testis and testicular cancer. These factors may partially explain the heterogeneity of the OR for this association in case-control studies relying on self-reports.
    背景与目标:
  • 【人MYCL2基因的睾丸特异性表达。】 复制标题 收藏 收藏
    DOI:10.1093/nar/19.11.3129 复制DOI
    作者列表:Robertson NG,Pomponio RJ,Mutter GL,Morton CC
    BACKGROUND & AIMS: :We have characterized the expression of MYCL2, an intronless X-linked gene related to MYCL1. RNase protection analysis of a panel of human normal and tumor tissues has revealed that MYCL2 is expressed almost exclusively in human adult normal testis; much lower levels of transcript were detected in one human lung adenocarcinoma. No MYCL2 transcript was found in human testis RNA obtained from second trimester fetuses. This observation suggests a germ cell rather than somatic cell origin of the transcript and possible developmental regulation of MYCL2. Northern blot analysis of poly(A)+ RNA from adult human normal testis with an antisense riboprobe revealed a transcript of approximately 4.8-kb, which is in agreement with the size predicted from the MYCL2 nucleotide sequence. Antisense transcripts were found spanning regions of MYCL2 corresponding to all three exons of MYCL1. No sizable open reading frame was seen for the MYCL2 antisense transcripts suggesting that they may represent either regulatory sequences or an intron of a gene encoded by the complementary strand. RNase protection assays and the 5' RACE protocol (Rapid Amplification of cDNA Ends) were used to address the localization of the transcription start site of the MYCL2 sense transcript and different putative promoters and transcription regulatory elements have been identified.
    背景与目标: : 我们已经表征了MYCL2的表达,MYCL2是与mycl1相关的无内含子X连锁基因。对一组人类正常和肿瘤组织的RNase保护分析表明,MYCL2几乎仅在人类成人正常睾丸中表达; 在一种人肺腺癌中检测到的转录本水平要低得多。在从妊娠中期胎儿获得的人睾丸RNA中未发现MYCL2转录本。此观察结果表明转录本的生殖细胞而不是体细胞起源以及mycl2的可能发育调控。用反义核糖探针对来自成人正常睾丸的poly(A)+ RNA进行的Northern印迹分析显示,转录物约为4.8-kb,这与从MYCL2核苷酸序列预测的大小一致。发现反义转录本跨越MYCL2的区域,对应于mycl1的所有三个外显子。对于MYCL2反义转录本,没有看到相当大的开放阅读框,表明它们可能代表由互补链编码的基因的调控序列或内含子。RNase保护试验和5' RACE方案 (cDNA末端的快速扩增) 用于解决MYCL2有义转录本的转录起始位点的定位,并且已经鉴定出不同的推定启动子和转录调控元件。
  • 【CABYR是肺癌中的一种新型癌症-睾丸抗原。】 复制标题 收藏 收藏
    DOI:10.1158/1078-0432.CCR-06-1742 复制DOI
    作者列表:Luo C,Xiao X,Liu D,Chen S,Li M,Xu A,Liu J,Gao S,Wu S,He D
    BACKGROUND & AIMS: PURPOSE:Cancer-testis (CT) antigens are often expressed in a proportion of tumors of various types. Their restricted normal tissue expression and immunogenicity make them potential targets for immunotherapy. CABYR is a calcium-binding tyrosine phosphorylation-regulated fibrous sheath protein initially reported to be testis specific and subsequently shown to be present in brain tumors. This study was to determine whether CABYR is a novel CT antigen in lung cancer. EXPERIMENTAL DESIGN:mRNA expression of CABYR-a/b (combination of CABYR-a and CABYR-b) and CABYR-c was examined in 36 lung cancer specimens, 14 cancer cell lines, and 1 normal cell line by conventional and real-time reverse transcription-PCR. Protein expression of CABYR was analyzed in 50 lung cancer tissues by immunohistochemistry. Antibodies specific to CABYR were analyzed in sera from 174 lung cancer patients and 60 healthy donors by ELISA and Western blot. RESULTS:mRNA expression of CABYR-a/b and CABYR-c was observed, respectively, in 13 and 15 of 36 lung cancer tissues as well as in 3 and 5 of 14 cancer cell lines, whereas neither of them was observed in adjacent noncancerous tissues or the normal cell line. Protein expression of CABYR-a/b and CABYR-c was observed, respectively, in 20 and 19 of 50 lung cancer tissues. IgG antibodies specific to CABYR-a/b and CABYR-c were detected, respectively, in 11% and 9% of sera from lung cancer patients but not from the 60 healthy donors. CONCLUSION:CABYR is a novel CT antigen in lung cancer and may be a promising target for immunotherapy for lung cancer patients.
    背景与目标:
  • 【野生动物前列腺和睾丸中的乳酸脱氢酶同工酶及一些组织学评论。】 复制标题 收藏 收藏
    DOI:10.1007/BF00256045 复制DOI
    作者列表:Van Camp K,Van Sande M
    BACKGROUND & AIMS: :The lactate dehydrogenase (LDH) isoenzyme pattern of prostate and of testis of 27 wild animals showed that in several species more than 5 isoenzymes are detected, with electrophoretic mobilities different to those found in humans. The LDH-X band, found in testis from mature humans is also observed in the testis of wild animals. However, in several species more than one LDH-X is found. The results obtained demonstrate their usefulness in phylogeny. The prostate gland and testis of the chimpanzee show the greatest resemblance to man. Histological examination of the prostate glands seems to correlate with the phylogenetical classification of the mammals studied.
    背景与目标: : 27种野生动物的前列腺和睾丸的乳酸脱氢酶 (LDH) 同工酶模式表明,在几种物种中检测到5种以上的同工酶,其电泳迁移率与人类不同。在野生动物的睾丸中也观察到在成熟人类的睾丸中发现的ldh-x带。但是,在几种物种中发现了一个以上的ldh-x。获得的结果证明了它们在系统发育中的有用性。黑猩猩的前列腺和睾丸与人类最相似。前列腺的组织学检查似乎与所研究哺乳动物的系统发育分类有关。
  • 【作者更正: 睾丸癌抗原可促进三阴性乳腺癌转移,并可在循环的细胞外囊泡中追踪。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-020-58045-z 复制DOI
    作者列表:Kannan A,Philley JV,Hertweck KL,Ndetan H,Singh KP,Sivakumar S,Wells RB,Vadlamudi RK,Dasgupta S
    BACKGROUND & AIMS: :An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    背景与目标: : 本文的修正案已经发表,可以通过本文顶部的链接进行访问。
  • 【癌症/睾丸抗原、北九州肺癌抗原-1和ABCD分层诊断胃癌。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v26.i4.424 复制DOI
    作者列表:Shida A,Fukuyama T,Futawatari N,Ohmiya H,Ichiki Y,Yamashita T,Nishi Y,Kobayashi N,Yamazaki H,Watanabe M,Takahashi Y
    BACKGROUND & AIMS: BACKGROUND:The ABCD stratification [(combination of serum pepsinogen (PG) levels and titers of antibody (immunoglobulin G, IgG) against Helicobacter pylori (H. pylori)] is effective for the classification of individuals at risk of developing gastric cancer (GC). The Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a Cancer/Testis antigen frequently expressed in GC. AIM:To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC. METHODS:We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors. The levels of serum PG I/PG II and IgG against H. pylori were measured. According to their serological status, the patients were classified into the four groups of the ABCD stratification. RESULTS:Of the 77 examined patients, 63 (81.8%) expressed KK-LC-1. The IgG titers of H. pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1 (P = 0.0289 and P = 0.0041, respectively). The expression of KK-LC-1 in group C [PG method (+)/H. pylori infection (+)] was as high as 93.9% high. KK-LC-1 was also detected in group A [-/-]. CONCLUSION:The KK-LC-1 expression in GC was associated with H. pylori infection and atrophic status, so that, KK-LC-1 may be a useful marker for the diagnosis of GC.
    背景与目标:
  • 【柴油机尾气颗粒干扰小鼠睾丸基因表达。】 复制标题 收藏 收藏
    DOI:10.1002/tox.20234 复制DOI
    作者列表:Mori T,Watanuki T,Kashiwagura T
    BACKGROUND & AIMS: :Inhalation of diesel exhaust particles (DEP) has been found to reduce sperm production. There is a possibility that DEP exposure elicits changes in gene expression in testis. To identify the alteration of gene expression resulting from DEP exposure, we constructed subtracted cDNA libraries from mouse testis using the suppression subtractive hybridization method. We isolated 16 candidate clones whose expression levels changed after exposure. Some of these candidates were highly similar to known testis-specific genes. Some of the clones also seemed to correlate with spermatogenesis. Northern blot analysis revealed that DEP exposure changed the expression levels of several clones in a dose-dependent manner. For example, the expression of clone R8, which was very similar to human XRRA1, increased by 2.3-fold in testis after DEP exposure. On the other hand, the expressions of long-chain acyl-CoA synthetase 6 (Acsl6) and serine/threonine kinase 35 reduced by 0.3-fold. These results indicated that some constituents of DEP alter gene expression in the testis.
    背景与目标: : 已发现吸入柴油废气颗粒 (DEP) 可减少精子的产生。DEP暴露可能会引起睾丸中基因表达的变化。为了鉴定由DEP暴露引起的基因表达的改变,我们使用抑制消减杂交方法从小鼠睾丸中构建了减去cDNA文库。我们分离出16个候选克隆,其表达水平在暴露后发生变化。其中一些候选基因与已知的睾丸特异性基因高度相似。一些克隆似乎也与精子发生有关。Northern印迹分析显示,DEP暴露以剂量依赖性方式改变了几个克隆的表达水平。例如,与人XRRA1非常相似的克隆R8的表达在DEP暴露后在睾丸中增加了2.3倍。另一方面,长链酰基辅酶a合成酶6 (Acsl6) 和丝氨酸/苏氨酸激酶35的表达降低了0.3倍。这些结果表明,DEP的某些成分改变了睾丸中的基因表达。
  • 【睾丸中的替代RNA剪接调节。】 复制标题 收藏 收藏
    DOI:10.1530/REP-06-0147 复制DOI
    作者列表:Elliott DJ,Grellscheid SN
    BACKGROUND & AIMS: :Alternative splicing regulation has been shown to be critically important for several developmental pathways. It is particularly prevalent in the testis, which is the site of an extensive adult developmental programme. Alternative splicing is controlled by a splicing code, in which transcripts respond to subtle cell type-specific variations in positive and negative trans-acting RNA-binding proteins according to their unique set of binding sites for these proteins. Because of their unique combinations of cis-acting sequence elements, specific transcripts are able to respond individually to this code. In this review, we discuss how this code may be deciphered in germ cells to mediate a splicing response.
    背景与目标: : 替代剪接调节已被证明对几种发育途径至关重要。它在睾丸中特别普遍,睾丸是广泛的成人发育计划的场所。选择性剪接由剪接代码控制,其中转录本根据其独特的结合位点集,对阳性和阴性反式作用RNA结合蛋白的细微细胞类型特异性变化做出反应。由于顺式作用序列元素的独特组合,因此特定的转录本能够单独响应此代码。在这篇综述中,我们讨论了如何在生殖细胞中破译该代码以介导剪接反应。
  • 【超声多普勒在诊断未降睾丸扭转中的关键验证。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Slijper N,Sukhotnik I,Toubi A,Mogilner J
    BACKGROUND & AIMS: BACKGROUND:Testicular torsion associated with undescended testis is uncommon but requires immediate treatment. Ultrasound Doppler is recognized as the preferred imaging modality for testicular torsion due to its high specificity, sensitivity and availability. OBJECTIVES:To determine the accuracy of ultrasound Doppler in diagnosis of torsion of undescended testis. METHODS:We describe three patients with known undescended testis who were admitted with groin pain and had preoperative ultrasound Doppler. The discrepancy between these and the intraoperative findings is discussed. RESULTS:In two patients incarcerated inguinal hernia was diagnosed with ultrasound Doppler; however, surgery revealed torsion of an undescended testis. In the third patient ultrasound Doppler diagnosed torsion of undescended testis, but at surgery incarcerated inguinal hernia was found, without evidence of testicular torsion. CONCLUSIONS:Torsion of undescended testis should be a clinical rather than radiologic diagnosis.
    背景与目标:
  • 【睾丸特异性因子CTCFL与H19印迹控制区甲基化中的蛋白甲基转移酶PRMT7协同作用。】 复制标题 收藏 收藏
    DOI:10.1371/journal.pbio.0040355 复制DOI
    作者列表:Jelinic P,Stehle JC,Shaw P
    BACKGROUND & AIMS: :Expression of imprinted genes is restricted to a single parental allele as a result of epigenetic regulation-DNA methylation and histone modifications. Igf2/H19 is a reciprocally imprinted locus exhibiting paternal Igf2 and maternal H19 expression. Their expression is regulated by a paternally methylated imprinting control region (ICR) located between the two genes. Although the de novo DNA methyltransferases have been shown to be necessary for the establishment of ICR methylation, the mechanism by which they are targeted to the region remains unknown. We demonstrate that CTCFL/BORIS, a paralog of CTCF, is an ICR-binding protein expressed during embryonic male germ cell development, coinciding with the timing of ICR methylation. PRMT7, a protein arginine methyltransferase with which CTCFL interacts, is also expressed during embryonic testis development. Symmetrical dimethyl arginine 3 of histone H4, a modification catalyzed by PRMT7, accumulates in germ cells during this developmental period. This modified histone is also found enriched in both H19 ICR and Gtl2 differentially methylated region (DMR) chromatin of testis by chromatin immunoprecipitation (ChIP) analysis. In vitro studies demonstrate that CTCFL stimulates the histone-methyltransferase activity of PRMT7 via interactions with both histones and PRMT7. Finally, H19 ICR methylation is demonstrated by nuclear co-injection of expression vectors encoding CTCFL, PRMT7, and the de novo DNA methyltransferases, Dnmt3a, -b and -L, in Xenopus oocytes. These results suggest that CTCFL and PRMT7 may play a role in male germline imprinted gene methylation.
    背景与目标: : 由于表观遗传调控-DNA甲基化和组蛋白修饰,印迹基因的表达仅限于单个亲本等位基因。Igf2/H19是一个相互印迹的基因座,表现出父本Igf2和母体H19表达。它们的表达受位于两个基因之间的父系甲基化印迹控制区 (ICR) 调节。尽管已证明从头DNA甲基转移酶是建立ICR甲基化所必需的,但它们靶向该区域的机制仍然未知。我们证明CTCFL/BORIS是CTCF的旁系,是在胚胎雄性生殖细胞发育过程中表达的ICR结合蛋白,与ICR甲基化的时间相吻合。PRMT7是一种与CTCFL相互作用的蛋白质精氨酸甲基转移酶,在胚胎睾丸发育过程中也表达。由PRMT7催化的组蛋白H4的对称二甲基精氨酸3在此发育时期积累在生殖细胞中。通过染色质免疫沉淀 (ChIP) 分析,该修饰的组蛋白也富含睾丸的H19 ICR和Gtl2差异甲基化区 (DMR) 染色质。体外研究表明,CTCFL通过与组蛋白和PRMT7的相互作用刺激PRMT7的组蛋白-甲基转移酶活性。最后,通过在非洲爪蟾卵母细胞中核共注射编码CTCFL,PRMT7和从头DNA甲基转移酶Dnmt3a,-b和-L的表达载体来证明H19 ICR甲基化。这些结果表明CTCFL和PRMT7可能在雄性种系印迹基因甲基化中起作用。
  • 【转移性睾丸腺癌的超微结构。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Mrak RE,Husain MM,Schaefer RF
    BACKGROUND & AIMS: :Adenocarcinoma of the rete testis is a rare tumor. We describe the ultrastructural appearance of a retroperitoneal adenocarcinoma metastatic from the rete testis, and compare this appearance with that of normal human rete testis. Both normal rete epithelium and the tumor showed deep, narrow nuclear invaginations with apparent nuclear lobulation; small, pleomorphic, electron-dense, membrane-bound granules in the basal cytoplasm; lipid droplets in the apical cytoplasm; and distinctive bulbous cytoplasmic projections along the apical surfaces of the cells. In addition, more general features of glandular tissue were seen. Features notable for their absence were mucin granules, microvilli containing filamentous cores, glycocalyx, and glycocalyceal bodies. The ultrastructural appearance was sufficiently distinctive to suggest that, in the proper clinical context, electron microscopy may serve to support a diagnosis of adenocarcinoma of the rete testis.
    背景与目标: 睾丸内腺癌是一种罕见的肿瘤。我们描述了从睾丸睾丸转移的腹膜后腺癌的超微结构外观,并将其与正常人睾丸的外观进行了比较。正常上皮和肿瘤均显示出深部狭窄的核内陷,并有明显的核分叶; 基底细胞质中的小,多形性,电子致密,膜结合颗粒; 顶端细胞质中的脂滴; 以及沿细胞顶端表面的独特球状细胞质突起。此外,还可以看到腺体组织的更一般特征。缺乏它们的特征是粘蛋白颗粒,含有丝状核的微绒毛,糖萼和糖萼体。超微结构的外观具有足够的独特性,表明在适当的临床背景下,电子显微镜检查可能有助于诊断睾丸腺癌。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录