Characterization of<i>HOX</i>gene expression in canine mammary tumour cell lines from spontaneous tumours

DeInnocentes, Patricia; Perry, Amie; Graff, Emily C.; Kabir, Farruk M. Lutful; Bird, Richard M.

doi:10.1111/vco.12062

Cited by 8 publications

(7 citation statements)

References 53 publications

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“…In the previous study, the HOX gene was overexpressed by investigating the spontaneously derived tumor-bearing canine breast cancer model. The expression profile was consistent with the oncogene-like features (HOXA1, HOXA13, HOXD4, HOXD9 and SIX1) [ 20 ]. It was also reported that HOX cluster genes promoted the proliferation and differentiation of neuroblastoma cells [ 21 ].…”

Section: Introductionmentioning

confidence: 56%

Clinicopathological analysis of HOXD4 expression in diffuse gliomas and its correlation with IDH mutations and 1p/19q co-deletion

et al. 2017

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BackgroundsHOX (homologous box) is known as the dominant gene of vertebrate growth and cell differentiation. Abnormal expression of HOX gene in various tumors has attracted the attention of scholars. As a component of HOX clusters, HOXD4 plays a controversial role in the tumorigenesis of central nervous system.ResultsThe data demonstrated that and the results demonstrated that HOXD4 was overexpressed in glioma tissues compared to that of normal brain tissues. patients with high HOXD4 expression had a significant shorter survival than those with low HOXD4 expression in total glioma cohort (p<0.001), WHO Grade II cohort (p=0.003) and Grade III cohort (p<0.001), but not in Grade IV cohort when OS (overall survival) was analyzed (p=0.216). The findings were confirmed by the large-scale omics data analysis including lower-grade glioma (LGG) and glioblastoma multiforme (GBM) in TCGA (the cancer genome atlas) and CGGA (Chinese glioma genome atlas). Moreover, it was revealed that the expression of HOXD4 have a significant impact on the OS of Grade IV glioma with IDH wild-type and 1p/19q intact according to TCGA data.MethodsClinicopathological analysis of HOXD4 expression in 453 glioma patients was performed in the current study. Expression of HOXD4 was evaluated by qPCR and immunohistochemical (IHC) staining. Univariate and multivariate analysis were conducted to investigate the prognostic role of HOXD4 in glioma patients.ConclusionsExpression of HOXD4 was closely related to the clinical outcomes of patients with gliomas, and HOXD4 may be a potential prognostic biomarker of gliomas.

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Section: Introductionmentioning

confidence: 56%

Clinicopathological analysis of HOXD4 expression in diffuse gliomas and its correlation with IDH mutations and 1p/19q co-deletion

et al. 2017

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“…HOXD9 is a little-studied homeobox gene known to be involved in the development of gynecological organs 36 and mammary gland maturation during pregnancy and lactation 37 . Previous reports indicate HOXD9 may behave as an oncogene in glioma 38 and breast cancer 39 . Consistent with this, in functional assays we showed that higher HOXD9 expression reduced apoptosis, increased proliferation under conditions of high cell density and enhances ectopic proliferation of cells in the absence of attachment to a substrate.…”

Section: Discussionmentioning

confidence: 94%

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Lawrenson¹,

Li²,

Kar³

et al. 2015

Nat Commun

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Genome-wide association studies have reported eleven regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (P<1.4×10−3, FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6×10−10 for risk variants (P<10−4) within 10kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.

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“…The development of disease composed of malignant mammary carcinomas in patients in both species demonstrates similar age-associations, as well as nutritional, environmental, and reproductive factors that correlate with tumorigenesis [73839]. Patients in both species also share similar genetics, histologic appearance, biological behavior, molecular targets, and therapeutic response to treatment [739]. Both human and canine breast cancers exhibit cellular heterogeneity within the tumor and its surrounding environment, and tumors readily develop resistance to existing treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Both species have remarkably similar natural histories, and the patient can die from metastatic disease if not treated effectively [1]. Canine mammary tumors (CMTs) have been characterized extensively, as a comparative model of human breast cancers, and have been shown to have similar genetic defects and phenotypes including hormone-dependence, similar malignant tissue types, and natural history [2345678910].…”

Section: Introductionmentioning

confidence: 99%

Autologous hybrid cell fusion vaccine in a spontaneous intermediate model of breast carcinoma

et al. 2019

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Breast cancer is among the most common malignancies affecting women and reproductively intact female dogs, resulting in death from metastatic disease if not treated effectively. To better manage the disease progression, canine mammary tumor (CMT) cells derived from malignant canine mammary cancers were fused to autologous dendritic cells (DCs) to produce living hybrid-cell fusion vaccines for canine patients diagnosed with spontaneous mammary carcinoma. The high-speed sorting of rare autologous canine patient DCs from the peripheral blood provides the autologous component of fusion vaccines, and fusion to major histocompatibility complex-unmatched CMT cells were produced at high rates. The vaccinations were delivered to each patient following a surgical resection 3 times at 3-week intervals in combination with immuno-stimulatory oligonucleotides and Gemcitabine adjunct therapy. The immunized patient animals survived 3.3-times longer (median survival 611 days) than the control patients (median survival 184 days) and also appeared to exhibit an enhanced quality of life. A comparison of vaccinated patients diagnosed with inflammatory mammary carcinoma resulted in a very short median survival (42 days), suggesting no effect of vaccination. The data showed that the development of autologous living DC-based vaccine strategies in patient animals designed to improve the management of canine mammary carcinoma can be successful and may allow an identification of the antigens that can be translatable to promote effective immunity in canine and human patients.

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Characterization ofHOXgene expression in canine mammary tumour cell lines from spontaneous tumours

Cited by 8 publications

References 53 publications

Clinicopathological analysis of HOXD4 expression in diffuse gliomas and its correlation with IDH mutations and 1p/19q co-deletion

Clinicopathological analysis of HOXD4 expression in diffuse gliomas and its correlation with IDH mutations and 1p/19q co-deletion

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Autologous hybrid cell fusion vaccine in a spontaneous intermediate model of breast carcinoma

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