Disease relevance of HOXB13

• HOXB13 induces growth suppression of prostate cancer cells as a repressor of hormone-activated androgen receptor signaling [1].
• Functionally, forced expression of HOXB13 drove colorectal cancer (CRC) cells into growth suppression [2].
• Expression in hyperproliferative skin conditions remained cytoplasmic with the exception of epidermis associated with Kaposi's sarcoma, which showed strong HOXB13 expression that was partially localized to the nucleus [3].
• Regulation of tumor invasion by HOXB13 gene overexpressed in human endometrial cancer [4].
• To investigate whether overexpression of HOXB13 is involved in invasion or metastasis of endometrial cancer, we transfected antisense HOXB13/pcDNA3.1+ plasmid vector into endometrial cancer AN3CA cells by electroporation and performed in vitro chemoinvasion assay [4].
• Taken together, our results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer [5].

High impact information on HOXB13

• Reexpression of either of two of the silenced genes, HOXB13 and SYK, resulted in reduced colony formation in vitro and diminished tumor formation in vivo, indicating that these genes function as tumor suppressors in melanoma [6].
• Western blot analysis demonstrated that HOXB13 down-regulates the expression of TCF-4 and its responsive genes, c-myc and cyclin D1 [7].
• HOXB13 homeodomain protein suppresses the growth of prostate cancer cells by the negative regulation of T-cell factor 4 [7].
• Expression of HOXB13 was forced in HOXB13-negative PC3 prostate cancer cells using a liposome-mediated gene transfer approach [7].
• Altogether, our data present a novel mechanism for the HOXB13-mediated repression of AR signaling, which can be interpreted to a growth-suppressive event [1].

Chemical compound and disease context of HOXB13

• In addition, administration of 17beta-estradiol induced time- and dose-dependent responses of the HOXB13 expression in endometrial cancer AN3CA cells [4].
• CONCLUSION: A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative, ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied [8].

Biological context of HOXB13

• However, the function of HOXB13 in normal cell growth and tumorigenesis is not yet known [7].
• Overexpression of HOXB13 further down-regulated the androgen-stimulated expression of prostate-specific antigen, and suppression of endogenous HOXB13 stimulated transactivation of AR [1].
• This study suggests that HOXB13, a transcription factor, functions as a cell growth suppressor by negatively regulating the expression of TCF-4, which eventually provides negative signals for cell proliferation [7].
• We initially isolated the HOXB13 gene from human fetal skin in experiments designed to identify candidate genes that regulate scarless fetal wound healing [3].
• This is the first description of the downregulation of HOXB13 in CRC and its mechanism of action is mediated through the regulation of TCF4 protein stability [2].

Anatomical context of HOXB13

• HOXB13 expression was decreased in wounded fetal tissue relative to unwounded fetal controls or wounded adult skin [9].
• Low-level HOXB13 protein expression was detected in adult skin and within the telogen hair follicle, and a portion of the residual signal in adult epidermis was nuclear [3].
• HOXB13 protein expression was detected throughout the developing epidermis, with weaker signal observed in the early developing dermis [3].
• Quantitative RT-PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates [10].
• OBJECTIVE: To analyze the presence of HOXB13 transcript expression in human minor salivary gland [11].

Regulatory relationships of HOXB13

• In prostate cancers, HOXB13 negatively regulates beta-catenin/TCF4-mediated transactivation and subsequently inhibits cell growth [2].
• Compared with the control clones, HOXB13-expressing PC3 cells exhibited significant inhibition of in vitro and in vivo cell growth with G1 cell cycle arrest mediated by the suppression of cyclin D1 expression [7].

Other interactions of HOXB13

• Our findings suggest that the expression of HOXB13, D9, D10, and HOXC cluster (HOXC9, C11-C13) genes might be an important step involved in cervical cancer [12].
• Thus both HOXB13 and PRX-2 are expressed in patterns consistent with roles in fetal skin development and cutaneous regeneration [9].
• Our results suggest that loss of HOXB13 may be an important event for colorectal cell transformation, considering that over 90% of colorectal tumours retain mutations in the APC/beta-catenin pathway [2].
• Interestingly, HOXB2, HOXB4, and HOXB13 gene expression was found only in tumor tissues [13].
• Antisense introduction followed by chemoinvasion assay using matrigel chamber demonstrated that SKOV3 cells introduced an antisense of each HOXB7 and HOXB13 showed 85% and 50% reduction of invasion ability compared to the parental SKOV3 cells, respectively [14].

Analytical, diagnostic and therapeutic context of HOXB13

• To study the role of HOXB13 in colorectal tumorigenesis, we evaluated the expression of HOXB13 in 53 colorectal tumours originated from the distal left colon to rectum with their matching normal tissues using quantitative RT-PCR analysis [2].
• MATERIAL AND METHODS: Ten-micrometer sections from frozen samples were evaluated employing non-radioactive in situ hybridization technique and HOXB13 mRNA probes [11].
• An expression signature predictive of disease-free survival was reduced to a two-gene ratio, HOXB13 versus IL17BR, which outperformed existing biomarkers [15].

References