Impact of homeobox genes in gastrointestinal cancer

Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal(GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1(CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett's esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.

Homeobox genes for embryo implantation: From mouse to human

The proper development of uterus to a state of receptivity and the attainment of implantation competency for blastocyst are 2 indispensable aspects for implantation,which is considered to be a critical event for successful pregnancy. Like many developmental processes, a large number of transcription factors, such as homeobox genes, have been shown to orchestrate this complicated but highly organized physiological process during implantation. In this review, we focus on progress in studies of the role of homeobox genes, especially the Hox and Msx gene families, during implantation, together with subsequent development of post-implantation uterus and related reproductive defects in both mouse models and humans, that have led to better understanding of how implantation is precisely regulated and provide new insights into infertility.

Effects of Phenylacetate on Cell Proliferation and Homeobox Genes Expression in the HCT-8 Colorectal Carcinoma Cell Line

To study the effects of phenylacetate （PA） on cell proliferation and homeobox （HOX） genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellular proliferation inhibition was evaluated by the MTT assay. Twenty-two HOX genes were divided into three groups （ P1, P2, P3） according to their primer sequences, and the samples of cells were analyzed for the HOX genes＇ mRNA expression by means of the semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. The level of the HOX genes＇ expression was expressed as the ratio expression rate of HOX gene to the β-actin. HCT-8 cells were treated with 1.0-5.0 mmol/L PA for 24-72 h. With the increase of the PA concentration or the prolongation of the treating time, the cell proliferation is inhibited in a dose- and time-dependent manner. The P1 group mRNA＊ expression（0. 5781 ±0. 0836） is significantly lower than that of the untreated group （0. 7701 ± 0. 0883 ） in HCT-8 cells （p 〈 0. 001 ）. Both the mRNA expressions of groups P2 （0. 3941 ± 0. 0819） and P3 （0. 5601 ± 0. 0736） in the PA treated group are significantly higher than those of the untreated groups P2（0. 1221±0. 0782） and P3 （0. 1806 ± 0. 0811 ） in HCT-8 cells（p 〈 0. 001）. PA could effectively inhibit cell proliferation by regulating the HOX genes expression and the mechanisms of the PA action are correlated with the transcription process in HCT-8 cells.

泛癌分析HOXA基因簇表达及预后意义

目的探讨HOXA基因簇中各蛋白编码基因和非编码基因在泛癌中的表达及对肿瘤预后评估的作用。方法使用NCBI网站GeneBank数据库分析HOXA基因簇中蛋白编码基因和非编码基因的组成及相互位置关系。应用UCSC数据库phasCons评分分析HOXA基因簇序列的保守性。基于美国阿拉巴马大学伯明翰分校创立的癌症组学数据UALCAN分析网站,评估HOXA基因簇转录的11个HOXA编码基因和6个非编码基因在24种癌症中的表达模式,Kaplan-Meier分析在泛癌中HOXA基因簇中蛋白编码基因和非编码基因表达与肿瘤预后的相关性。结果人HOXA基因簇由11个蛋白编码基因和6个已被注释的非编码基因组成,分别位于染色体7p15.2的DNA负链和正链上。HOXA基因簇各蛋白编码基因进化十分保守,而非编码基因的保守性低于编码基因。24种癌症的差异分析结果显示HOXA基因簇转录的蛋白编码基因及非编码基因在肿瘤组织中的表达与正常对照组织有差异,表达模式具有组织器官特异性。生存分析提示HOXA基因簇中蛋白编码基因和非编码基因低表达有利于肾透明细胞癌、子宫内膜癌、肺腺癌、直肠腺癌、胃腺癌、肾嫌色细胞癌、头颈部鳞状细胞癌、甲状腺癌及肾乳头状细胞癌的预后。结论HOXA基因簇成员可能是泛癌诊断和预后的重要分子生物标志物。

Role of Hox genes in stem cell differentiation

Hox genes are an evolutionary highly conserved gene family. They determine the anterior-posterior body axis in bilateral organisms and influence the developmental fate of cells. Embryonic stem cells are usually devoidof any Hox gene expression, but these transcription factors are activated in varying spatial and temporal patterns defining the development of various body regions. In the adult body, Hox genes are among others responsible for driving the differentiation of tissue stem cells towards their respective lineages in order to repair and maintain the correct function of tissues and organs. Due to their involvement in the embryonic and adult body, they have been suggested to be useable for improving stem cell differentiations in vitro and in vivo. In many studies Hox genes have been found as driving factors in stem cell differentiation towards adipogenesis, in lineages involved in bone and joint formation, mainly chondrogenesis and osteogenesis, in cardiovascular lineages including endothelial and smooth muscle cell differentiations, and in neurogenesis. As life expectancy is rising, the demand for tissue reconstruction continues to increase. Stem cells have become an increasingly popular choice for creating therapies in regenerative medicine due to their self-renewal and differentiation potential. Especially mesenchymal stem cells are used more and more frequently due to their easy handling and accessibility, combined with a low tumorgenicity and little ethical concerns. This review therefore intends to summarize to date known correlations between natural Hox gene expression patterns in body tissues and during the differentiation of various stem cells towards their respective lineages with a major focus on mesenchymal stem cell differentiations. This overview shall help to understand the complex interactions of Hox genes and differentiation processes all over the body as well as in vitro for further improvement of stem cell treatments in future regenerative medicine approaches.

Comprehensive analysis of distal-less homeobox family gene expression in colon cancer

BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.

Hox genes and study of Hox genes in crustacean

Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.

Production of homeobox A10 gene transgenic pigs by somatic cell nuclear transfer

Homeobox A10(Hoxa10) gene is one of the most important candidate genes associated with the reproductive performance of humans and mice. Overexpression of Hoxa10 in mouse endometrium can increase litter size. Moreover, Hoxa10 plays a key role in regulating the embryo implantation of sows. This study aimed to generate transgenic pigs using Hoxa10 via somatic cell nuclear transfer(SCNT). We established seven Hoxa10-transgenic cell lines, and two of the cell lines were selected as nuclear donors for the transfer. A total of 1 270 cloned embryos were generated and transferred to five surrogate mothers(Landrace×Yorkshire). Eight cloned male piglets were produced including one with cryptorchidism. Six transgenic piglets grew up healthy and produced 56 offspring. Finally, we obtained six transgenic male pigs and 26 transgenic positive offspring that can be used to further study the regulatory mechanism of Hoxa10 on the reproductive performance of pigs.

Overexpression of the Six1 Homeobox Gene Is Associated with Diffuse Peritoneal Spread and Larger Residual Disease after Maximal Cytoreductive Effort in Advanced Ovarian Cancer

Study Design: Between January 2003 and June 2009, we collected fresh tumor and extracted high-quality RNA from the omental/peritoneal metastases of 47 patients with stage IIB-IV ovarian cancer. Clinical data were abstracted from the patients’ medical records. Expression of Six1 level by quantitative RT-PCR was compared with preoperative factors and intraoperative findings using the χ2 test and the Fisher exact test. The effect of Six1 elevation on survival was assessed with the Kaplan/Meier method. Results: The mean age of patients enrolled was 60 (range 33 - 84). The histological subtypes were 77% serous (36/47), 11% endometrioid (5/47), 4% mucinous (2/47), and 4% clear cell (2/47). Eighty-one percent were optimally cytoreduced. Median Six1 expression for the samples was 114 fg/ng 18S rRNA and Six1 overexpression, defined as >300 fg/ng 18S rRNA, was observed in 19% of tumors. Six1 expression above sample median was associated with peritoneal disease (p = 0.049) and inability to optimally cytoreduce (p = 0.02). Six1 overexpression was associated with worsened survival in the high grade serous subgroup (43 months versus 71 months, p = 0.039 Log Rank test). Conclusions: Elevated levels of Six1 predict peritoneal disease and larger residual tumor after maximal cytoreductive effort. Prospective prediction of surgical cytoreduction using a combination of Six1 expression, included with other factors, is currently being evaluated.

HOXA9和LRP6在甲状腺癌中的表达及其在预后评估中的价值

目的探讨甲状腺癌组织中同源盒基因A9(HOXA9)、低密度脂蛋白受体相关蛋白6(LRP6)表达情况及其在预后评估中价值。方法收集山东省菏泽市立医院2018年1月至2020年1月150例甲状腺癌患者术中切除的癌组织(TC组),另以同期100例甲状腺瘤患者术中切除的组织为对照(腺瘤组)。免疫组化法检测组织HOXA9、LRP6蛋白表达,分析HOXA9、LRP6蛋白表达与临床病理特征关系。Kaplan-Meier法分析HOXA9、LRP6蛋白表达与生存率关系。甲状腺癌患者预后影响因素利用COX回归模型。结果TC组HOXA9阳性表达率(72.67%vs 16.00%)、LRP6阳性表达率(68.67%vs 14.00%)明显高于腺瘤组(P<0.05)。经卡方检验以及GEPIA数据库检索发现,甲状腺癌组织HOXA9与LRP6表达水平呈正相关(P<0.05)。HOXA9、LRP6阳性表达者临床分期为Ⅲ期、有淋巴结转移、细胞低分化者占比高于HOXA9、LRP6阴性表达(P<0.05)。HOXA9阳性表达总生存率(72.48%vs 92.68%)、LRP6阳性表达总生存率(71.84%vs 91.49%)低于HOXA9阴性表达、LRP6阴性表达(χ^(2)=6.829、6.508,P=0.009、0.011)。COX回归分析显示,临床分期Ⅲ期、HOXA9阳性表达、淋巴结转移、LRP6阳性表达是甲状腺癌患者不良预后的影响因素(P<0.05)。结论甲状腺癌组织中HOXA9、LRP6呈高表达,与临床病理特征及预后有关,可用于评估甲状腺癌预后指标。

疏肝补肾汤联合腹腔镜手术对难治性多囊卵巢综合征患者卵巢体积、血清HOXA10表达及妊娠率的影响

【目的】探讨疏肝补肾汤联合腹腔镜手术对难治性多囊卵巢综合征(PCOS)患者的卵巢体积、血清同源框基因A10(HOXA10)表达及妊娠率的影响。【方法】将80例肝郁肾虚型难治性PCOS患者随机分为观察组和对照组,每组各40例。对照组给予常规腹腔镜手术和常规药物治疗,观察组在对照组的基础上加用疏肝补肾汤治疗,1个月经周期为1个疗程,连续治疗3个疗程。观察2组患者治疗前后中医证候积分、卵巢体积、卵泡直径、血清HOXA10表达及性激素[黄体生成素(LH)、雌二醇(E2)、孕酮(P)、促卵泡生成素(FSH)和睾酮]水平的变化情况,以及2组患者随访半年的妊娠情况。【结果】(1)治疗后,2组患者的卵巢体积均呈现不同程度的缩小(P<0.05),卵泡直径均呈现不同程度的增加(P<0.05),且观察组对卵巢体积的缩小幅度及对卵泡直径的增加幅度均明显优于对照组(P<0.01)。(2)治疗后,2组患者的LH、FSH、睾酮水平均较治疗前明显降低(P<0.05),HOXA10、E2、P水平均较治疗前明显升高(P<0.05),且观察组对LH、FSH、睾酮水平的降低幅度及对HOXA10、E2、P水平的升高幅度均明显优于对照组(P<0.05或P<0.01)。(3)治疗后,2组患者的月经量异常、月经周期异常、腰膝酸软、舌质暗红、脉沉涩等各项中医证候积分及总积分均较治疗前明显降低(P<0.05),且观察组对各项中医证候积分及总积分的降低幅度均明显优于对照组,差异均有统计学意义(P<0.01)。(4)观察组的妊娠率为55.00%(22/40),明显高于对照组的32.50%(13/40),差异有统计学意义(P<0.05)。【结论】疏肝补肾汤联合腹腔镜手术治疗肝郁肾虚型难治性PCOS,可有效改善患者的卵巢功能,促进机体性激素水平恢复正常,提高HOXA10表达水平,改善患者的子宫内膜容受性,提高患者的妊娠率。

雌/孕激素受体和HOXA-9基因在输卵管和异位妊娠输卵管中的表达

目的:探讨雌激素受体(ER)、孕激素受体(PR)和HOXA-9基因在人输卵管中的表达及与输卵管妊娠的关系。方法:采用免疫组化和原位杂交方法对34例正常输卵管和38例妊娠输卵管黏膜中ER、PR和HOXA-9基因表达进行研究。结果:ER、PR在正常增生期和分泌期输卵管黏膜上皮中的表达率较高;在妊娠输卵管黏膜上皮中的表达率明显下降(P<0.01)。HOXA-9基因在正常增生期输卵管中的表达率较高,分泌期输卵管中表达降低,而在妊娠输卵管中表达率又有所增高(高于分泌期输卵管的表达率,P<0.05)。结论:ER、PR在输卵管黏膜上皮中的表达下降和HOXA-9基因表达增强与输卵管妊娠密切相关;在正常分泌期输卵管黏膜上皮中,ER、PR表达水平上调和HOXA-9基因表达下调可能起着屏障作用,防止输卵管着床的发生。

Homeobox基因对毛囊生长发育作用机制的研究进展

Homeobox(Hox)基因作为一种重要转录因子,在调节动物体轴发育方面发挥着重要的作用。自Hoxc13基因被首次证明与毛囊生长发育有密切关系后,Hox基因家族其他成员也逐渐被认为在毛囊生长发育与周期变化过程中充当着一个重要角色。作者综述了Hox基因在毛囊生长中的作用机理,为今后绒毛用动物相关领域研究提供思路。

种植窗口期人子宫内膜组织中ER、PR及HOXA-11的表达

目的:探讨雌孕激素受体(ER、PR)及同源框基因-11(HOXA-11)在人子宫内膜种植窗口期的表达。方法:采用免疫组化和RT-PCR方法检测ER、PR及HOXA-11在拟行IVF-ET患者排卵后子宫内膜种植窗口期的表达。按IVF-ET后是否妊娠将153例因输卵管因素不孕的患者分为未妊娠组(n=86)和妊娠组(n=67)。结果:免疫组化结果显示PR和HOXA-11在妊娠组腺上皮细胞中的表达均低于未妊娠组(P均<0.001),在间质细胞中的表达均高于未妊娠组(P均<0.001)。RT-PCR结果显示妊娠组子宫内膜ER、PR及HOXA-11 mRNA的相对表达量均高于未妊娠组(P均<0.05)。P水平与腺上皮、间质PR及腺上皮HOXA-11蛋白表达有关(P均<0.05)。结论:种植窗口期内膜腺上皮PR、HOXA-11表达下调和间质细胞PR、HOXA-11表达上调的失败可能是导致子宫内膜容受性下降的原因之一。

不明原因不孕妇女分泌期子宫内膜Hoxa-10mRNA表达意义的研究

目的 :探讨不明原因不孕与子宫内膜Hoxa 10基因表达的关系。方法 :采用核酸原位杂交技术 ,以Hox a 10mRNA寡核苷酸为探针进行检测。结果 :不明原因不孕组分泌早中期子宫内膜上Hoxa 10mRNA表达的灰度阳性单位 (PU)值无显著差异 ;正常生育组分泌中期子宫内膜上Hoxa 10mRNA表达的PU值显著高于分泌早期 ;不孕组分泌中期子宫内膜上Hoxa 10mRNA表达的PU值显著低于同期正常组。结论 :子宫内膜Hoxa 10基因在分泌中期的高表达可能和子宫内膜容受力密切相关 ,其表达缺陷可能是导致不明原因不孕的重要原因之一。

玉米大斑病菌Homeobox转录因子家族全基因组鉴定及其表达规律分析

【目的】从全基因组水平上鉴定玉米大斑病菌(Setosphaeria turcica)Homeobox转录因子家族及其分布,阐明该家族的序列及进化特征,分析该家族基因在病菌不同生长发育时期的表达规律。【方法】利用生物信息学手段搜索玉米大斑病菌全基因组数据库,鉴定Homeobox转录因子家族;采用MEGA 5.0软件进行系统进化树分析;利用在线工具GSDS(gene structure display server)(http://gsds1.cbi.pku.edu.cn/index.php)绘制基因结构图;利用Clustal X 1.83软件分析Homeobox保守结构域(HOX保守结构域)的氨基酸序列特征;利用SOPMA(https://npsa-prabi.ibcp.fr/cgi-bin/npsa_automat.plpage=npsa_sopma.html)对Homeobox蛋白的二级结构进行在线预测;利用实时荧光定量PCR(q RT-PCR)技术分析Homeobox转录因子家族在病菌不同发育时期的表达模式。【结果】在玉米大斑病菌中鉴定了8个Homeobox转录因子家族成员(St HTF1-8),根据基因结构及系统进化特征将其分为4类;亚细胞定位预测分析表明,这8个蛋白全部定位在细胞核中;该家族成员均含有HOX保守结构域,其二级结构具有特征性的"螺旋-转角-螺旋"(helix-turn-helix)结构;利用q RT-PCR技术对该家族成员在菌丝、分生孢子形成、芽管形成、附着胞及侵入丝形成等5个时期的表达规律分析,发现不同基因在病菌不同发育时期具有不同的表达水平,其中St HTF1在菌丝发育、分生孢子及附着胞形成等3个时期的表达水平相对较高,St HTF3、St HTF4在分生孢子形成时期表达水平最高,St HTF6在芽管形成时期的表达水平最高,St HTF2、St HTF5、St HTF7和St HTF8在附着胞形成时期的表达水平均较高。【结论】玉米大斑病菌包括Homeobox转录因子家族包含8个成员,在进化上分为4大类,全部成员均分布在细胞核内,其编码蛋白质均含有保守的HOX结构域及"螺旋-转角-螺旋"空间结构;该基因家族成员在病菌不同发育时期呈现不同的表达规律。

内蒙古绒山羊Homeobox基因片段的克隆与序列分析

根据已公布的Hom eobox基因氨基酸序列保守区设计简并引物,利用PCR技术从内蒙古绒山羊血液基因组DNA中扩增Hom eobox基因家族成员。目的基因片段纯化后连接到pGEM-T载体上,经鉴定得到重组质粒。将110个重组质粒进行测序,测序结果通过与GenBank中序列比对分析,确定86条序列为Hom eobox基因,得到14个Hom eobox基因家族成员:Hoxa4,Hoxa5,Hoxa6,Hoxa7,Hoxb1,Hoxb2,Hoxb3,Hoxb6,Hoxb7,Hoxc6,Hoxd1,Hoxd3,Gbx1,Gbx2。每个基因片段由117个核苷酸组成,编码39个氨基酸。氨基酸序列非常保守,和其他物种的同源性非常高。

原位杂交检测同源框基因HoxA11在人月经周期子宫内膜的表达

了解 Hox A1 1基因在人月经周期子宫内膜的表达及变化 ,探索该基因对正常内膜周期的调节功能。应用地高辛标记的 RNA探针进行原位杂交。 Hox A1 1基因主要在内膜间质细胞中表达 ,增殖期与分泌期比较未见明显差异。腺上皮细胞中 Hox A1 1基因的表达量虽较间质细胞少 ,但有明显的周期性变化 ,以增生殖期腺上皮细胞表达量较高 ,分泌早期开始下降 ,到分泌中晚期表达量极低或不表达。Hox A1 1基因在月经周期人子宫内膜中的这种表达时空的变化与孕酮受体 (PR)非常相似 ,提示 Hox A1 1基因的表达与卵巢激素及其受体的调控有着密切的关系 ,Hox A1 1在分泌中期内膜腺上皮中表达下降是内膜分化的重要指标志。

HOXA-11基因与不孕及妊娠失败关系的研究

目的 :研究HOXA 11基因与不孕及妊娠失败的关系。方法 :选择 4 1例不明原因不孕症患者及 30例难免流产患者 ,同时选择 2 8例正常未孕者及 18例正常早期妊娠者分别作为对照组 ,留取子宫内膜或蜕膜组织。子宫内膜标本通过组织学检查分为增生期或分泌期。难免流产及正常妊娠组均妊娠 6～ 9周。采用原位杂交方法检测所有子宫内膜或蜕膜组织中的HOXA 11基因mRNA的表达。结果 :整个月经周期子宫内膜腺上皮细胞及间质细胞中均有HOXA 11基因mRNA表达 ,并因月经周期不同而有所波动。HOXA 11基因mRNA在分泌中晚期子宫内膜间质细胞中阳性表达率为 10 0 % ,在增生期子宫内膜间质细胞中的阳性表达率为 6 3.6 % ,差异有显著性 (P <0 .0 5 ) ;在不明原因不孕症患者中HOXA 11基因失去了它在正常子宫内膜表达的周期性变化 ,而且基因表达缺失明显。HOX A 11基因在正常增生期及分泌期子宫内膜腺上皮细胞或间质细胞中的阳性表达率分别为90 .9%、82 .4 %和 6 3.6 %、10 0 % ,在不孕症增生期及分泌期子宫内膜两种细胞的阳性表达率分别为 38.9%、4 7.8%和 2 2 .2 %、39.1% ,两组分别比较 ,差异均有显著性 (P <0 .0 5 ) ;HOXA 11基因在正常早期妊娠蜕膜细胞中持续表达 ,其阳性表达率均为 10 0 % 。

HL-60细胞内同源盒HOXA1、cDNA基因的克隆

目的：研究同源盒ＨＯＸ基因的表达在ＡＴＲＡ诱导白血病细胞分化中的作用。方法：利用我们建立的一种高效、简单的ｃＤＮＡ克隆方法－ＨＯＸ家庭基因指纹图技术，克隆ＨＬ－６０细胞内的ＨＯＸｃＤＮＡ基因。采用半定量ＲＴ－ＰＣＲ技术初步探讨ＡＴＲＡ对所克隆的ＨＯＸ基因表达的影响。结果：筛选出一个在ＨＬ－６０细胞内有表达的同源盒基因一ＨＯＸＡＩ基因ｃＤＮＡ片段，初步研究证实，此基因的ｍＲＮＡ水平在ＡＴＲＡ的作用下被上调。结论：ＡＴＲＡ可诱导ＨＬ－６０细胞内ＨＯＸＡ１基因表达增强。提示在ＡＴＲＡ诱导细胞分化而治疗恶性肿瘤的分子机制中，包括上调ＨＯＸＡ１基因表达而致白血病细胞分化成熟。