Disease relevance of HOXB7

• In this study, we demonstrated that HOXB7, one member of this family, behaved as a transactivator in breast cancer cells [1].
• HOXB7 constitutively activates basic fibroblast growth factor in melanomas [2].
• Several melanomas, carcinomas, glioblastomas and leukemias showed coordinated expression of HOXB7 and bFGF with exception of the SkBr3 mammary carcinoma that was negative for both [3].
• These results reveal HOXB7 as a tumor antigen whose up-regulated expression could play a significant role in promoting growth and development of ovarian carcinomas [4].
• Microarray analyses of microdissected epithelial cells from bone metastasis revealed a HOXB7 overexpression that was 3-fold higher than in primary breast carcinomas and 18-fold higher compared with normal breast [5].

High impact information on HOXB7

• Furthermore, HOXB7 overexpression increased intracellular accumulation and secretion of basic fibroblast growth factor, a potent angiogenic and mitogenic factor [4].
• Overexpression of HOXB7 in immortalized normal ovarian surface epithelial cells dramatically enhanced cellular proliferation [4].
• ELISAs using purified recombinant HOXB7 protein revealed significant serologic reactivity to HOXB7 in 13 of 39 ovarian cancer patients and in only one of 29 healthy women (P < 0.0001) [4].
• Seven clones corresponding to the homeobox gene HOXB7 were isolated [4].
• Using four homeobox probes from the HOX2 locus and a previously undescribed homeobox cDNA (PL1), we screened mRNAs from 18 human leukemic cell lines representing erythroid, myeloid, and T- and B-cell lineages [6].

Biological context of HOXB7

• CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein [1].
• These novel findings indicate a key role for constitutive HOXB7 expression in melanoma cell proliferation via bFGF [2].
• Band shift and cotransfection experiments showed that HOXB7 directly transactivates the hFGF gene through one out of five putative homeodomain binding sites present in its promoter [2].
• In transient transfection experiments, IkappaB-alpha markedly increased HOXB7-dependent transcription from a reporter plasmid containing a homeodomain consensus-binding sequence [7].
• To explore the role of HOXB7 in myeloid hematopoiesis, a number of mutations and deletions in the gene were constructed that targeted sequences with known functions or in regions that had not been examined previously [8].

Anatomical context of HOXB7

• HOXB7 is expressed from primordial and early primary stage follicles through to germinal vesicle (GV) oocytes [9].
• Treatment of melanoma cell lines with antisense oligomers targeting HOXB7 mRNA markedly inhibited cell proliferation and specifically abolished expression of basic fibroblast growth factor (bFGF) mRNA [2].
• The HOXB7 gene was constitutively expressed in all 25 melanoma cell lines and analyzed under both normal and serum-starved conditions, as well as in in vivo primary and metastatic melanoma cells; conversely, HOXB7 was expressed in proliferating but not quiescent normal melanocytes [2].
• Comparison of tumor nodules for vascularization by CD-31 and CD-34 immunostaining revealed an increased number of blood vessels in tumors expressing HOXB7 [10].
• Hematopoietic progenitor/stem cells (HPCs/HSCs) purified from human adult peripheral blood (PB) were triggered into cycling, retrovirally transduced with HOXB7 and then functionally assayed in vitro [11].

Associations of HOXB7 with chemical compounds

• Moreover, trichostatin A, a deacetylase inhibitor, strongly enhanced the transcriptional properties of HOXB7 [1].
• We investigated whether high glucose alters Pax-2 gene expression and aimed to delineate its underlying mechanism(s) of action using both in vitro (mouse embryonic mesenchymal epithelial cells (MK4) and ex vivo (kidney explant from Hoxb7-green florescent protein (GFP) mice) approaches [12].

Physical interactions of HOXB7

• HOXB7 physically interacted both in vitro and in vivo with the coactivator CREB-binding protein (CBP) [1].
• In addition, transient co-transfection experiments illustrated that both HOXC6 transcripts encode gene products that repress transcription from a HOX binding sequence in MDA-MB231 cells and co-operate with other HOX gene products such as HOXB7 on their target genes [13].
• Cell transfection and site-specific mutagenesis demonstrated Sp1/Sp3, NF-Y, YY1 and USF-1 binding to be functional and fundamental in driving HOXB7 expression [14].

Regulatory relationships of HOXB7

• Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation [11].

Other interactions of HOXB7

• We used monoclonal antibodies to study the distribution of three homeoproteins, namely HOXB7, HOXC6 and HOXD4 [15].
• This interaction led to an enhanced transactivating potential and required the N-terminal of HOXB7 as well as two domains located at the C-terminal part of CBP [1].
• HOX genes function in groups, and we found that HOXA5 and HOXB7 were also down-regulated by phorbol ester [16].
• Since some genes (HOXB2, HOXB4, HOXB7) were always inactive when unmethylated, this unexpected relationship might indicate their key function(s) in the HOX gene network [17].
• This study reports the results of a comparative sequencing study in higher primates, focusing on the intergenic region located between HOXB6 and HOXB7 [18].

Analytical, diagnostic and therapeutic context of HOXB7

• Xenograft into athymic nude mice showed that SkBr3/HOXB7 cells developed tumors in mice, either irradiated or not, whereas parental SkBr3 cells did not show any tumor take unless mice were sublethally irradiated [10].
• Because HOXB7 seems to play an important role in tumor proliferation and progression, the analysis of its regulatory sequences might represent an important step for gene targeting according to a new therapeutic strategy [14].
• Molecular cloning of a mutated HOXB7 cDNA encoding a truncated transactivating homeodomain-containing protein [19].
• To examine whether overexpressed HOX genes regulate invasion of ovarian cancer cells directly, we introduced an antisense DNA fragment of overexpressed HOXB7 and HOXB13, and HOXC5 that did not show overexpression into SKOV3 cells by electroporation [20].
• In the present study real-time reverse transcription polymerase chain reaction (RT-PCR) assays for the detection of human aspartyl (asparaginyl) beta-hydroxylase (HAAH) and homeobox B7 (HoxB7) mRNA from intraductal brush cytology specimens were established [21].

References