Disease relevance of HOXA10

• Thrombin and interleukin-1beta regulate HOXA10 expression in human term decidual cells: implications for preterm labor [1].
• A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias [2].
• HOXA10 deregulation also severely perturbed the differentiation of human progenitors in vivo, reducing B-cell development by 70% in repopulated NOD/SCID mice and enhancing myelopoiesis in the transduced compartment [3].
• We investigated whether HOXA10 expression is deregulated in endometrial carcinomas, and how counteracting this aberrant expression modifies tumor behavior [4].
• We have previously shown that up-regulation of HOXA10 in periimplantation endometrium fails to occur in women with endometriosis [5].

High impact information on HOXA10

• In contrast, Hoxa10 and Hoxa11 induced morphogenesis of endometrioid-like and mucinous-like EOCs, respectively [6].
• This coincides spatially and temporally with expression of maternal Hoxa10 in distal oviductal and uterine epithelium [7].
• Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice [7].
• In addition, non-tissue-specific protein-promoter interactions involving the Sp1 transcription factor are necessary for hPL transcription initiation [8].
• The hPL enhancer is bound by multiple proteins including at least one placental specific protein that interacts with a TEF-1 motif [8].

Chemical compound and disease context of HOXA10

• The dramatic decrease of HOXA10 in response to IL-1beta or thrombin may contribute to progestin resistance in preterm labor, mimicking progesterone resistance seen in Hoxa10(-/-) mice [1].
• Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2-PL) gene therapy [9].
• Little or no difference was seen in luminal, glandular or endothelial HOXA-10 expression but a significant reduction in stroma HOXA-10 expression was noted in women with endometriosis [10].
• MnSOD-Plasmid Liposome (MnSOD-PL) intraoral gene therapy has been demonstrated to decrease normal tissue toxicity and also improve survival in mice with orthotopic SCC-VII squamous cell tumors on the floor of the mouth [11].

Biological context of HOXA10

• Deletional analysis of the EMX2 5' regulatory region revealed that a 150-bp element mediated transcriptional repression when cotransfected with pcDNA3.1/HOXA10 in transient-transfection assays [12].
• Binding of HOXA10 protein to this element was demonstrated by electrophoretic mobility shift assay and further localized to a consensus HOXA10 binding site within this element by DNase I footprinting [12].
• The glandular expression of HOXA10 and Meis1 was menstrual cycle stage specific, whereas glandular Pbx2 expression did not vary [13].
• CONCLUSION: The expression of HOXA10 protein at term indicates that it may have a role in maintaining decidual cell phenotype and pregnancy [1].
• Reporter gene studies reveal that FKHR stimulates both baboon and human IGFBP-1 promoter activity, whereas HOXA10 alone has a relatively weak effect [14].

Anatomical context of HOXA10

• To explore if these patterns reflect different functional activities, we have retrovirally engineered the overexpression of a 5'-located gene, HOXA10, in murine bone marrow cells and demonstrate effects strikingly different from those induced by overexpression of a 3'-located gene, HOXB4 [15].
• We have analyzed the expression of homeoproteins of the HOX family in resting and activated lymphoid cells and in neoplastic lymphoid cell lines by the use of monoclonal antibodies (MoAbs) already shown to react with the homeoproteins HOXA10, HOXC6, and HOXD4, respectively [16].
• Here we demonstrate the expression of Pbx and Meis family cofactors in the human endometrium and their interaction with HOXA10 [13].
• We have recently demonstrated that HOXA10 is expressed in the adult human uterus [17].
• Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells [18].

Associations of HOXA10 with chemical compounds

• HOXA10 was further analyzed because of its association with progesterone responsiveness [1].
• OBJECTIVE: We hypothesized that IL-1beta or thrombin would decrease HOXA10 expression, contributing to the progestin-resistant environment [1].
• After E(2) plus medroxyprogesterone acetate treatment, IL-1beta and thrombin resulted in an 86 and 72% decrease in HOXA10 mRNA, respectively [1].
• Expression of HOXA10 in cultured endometrial cells was stimulated by estrogen or progesterone [17].
• A 41-bp segment (Region A) showed highest affinity binding to HOXA10 protein [19].

Physical interactions of HOXA10

• Ablation of the Pbx binding site, but not ablation of the HOXA10 binding site in EMX2, resulted in loss of dimer binding [13].

Regulatory relationships of HOXA10

• These studies show that FKHR and HOXA10 interact directly and can function cooperatively to stimulate IGFBP-1 promoter activity in endometrial cells and perhaps in other settings [14].
• HOXA10 regulates p53 expression and matrigel invasion in human breast cancer cells [20].
• Furthermore, aberrant HOXA10 expression almost completely blocked erythroid differentiation in methylcellulose (P < .02) [3].
• HOXA10 is expressed in all types of acute myelogenous leukemia (AML) with the notable exception of acute promyelocytic leukemia (AML-M3) [21].
• In conclusion, HOXA-10 is a hormone-regulated endometrial transcription factor that appears to be responsive to both ovarian steroids and relaxin [10].

Other interactions of HOXA10

• Finally, our observation also supports the previous suggested role of HOXA10 and HOXA11 in normal thymocyte development [2].
• When FKHR and HOXA10 are expressed together, promoter activity is markedly up-regulated, which is indicative of cooperativity [14].
• Herein, we took advantage of the strong transforming potential of NUP98-HOXD13 or NUP98-HOXA10 to establish preleukemic myeloid lines from bone marrow cells that faithfully replicate the first step of Hox-induced leukemogenesis [22].
• Real time quantitative PCR analysis for all HOXA genes revealed high levels of HOXA10 and HOXA11 expression in all inv(7) positive cases [2].
• HOXA10, a homeobox transcription factor, is important in the decidualization process [14].

Analytical, diagnostic and therapeutic context of HOXA10

• To examine expression of HOXA10 during the menstrual cycle, Northern blot analysis and in situ hybridization were performed [17].
• This novel animal model can be used to identify the target genes of HOXA10 and better clarify the specific role of HOXA10 in normal and malignant hematopoiesis [23].
• In human uterine or cervical cell cultures, DES induces HOXA9 or HOXA10 gene expression, respectively, to levels approximately twofold that induced by estradiol [24].
• After incubation, the cells were lysed in Trizol, and total RNA was extracted and analyzed by Northern blot using a 32P-labeled HOXA10 riboprobe [25].
• Immunocytochemistry and transient expression of the HOXA10 tagged with green fluorescence protein revealed that there were no differences in the HOXA10 subcellular localization between the induced and non-induced ESC [26].

References