Overexpression Of HOXB13 Research Articles

Regulation of tumor invasion by HOXB13 gene overexpressed in human endometrial cancer

During the last two decades, a group of homeobox-containing genes, the HOX gene family, has been studied both in the context of embryonic development and neoplasia. In particular, there is accumulating evidence of the involvement of HOX abnormalities in a variety of malignancies, including breast cancer. However, little is known about the association of HOX genes with endometrial cancer, which is the most common malignancy of the female genital tract and is thought to be dependent on estrogen, like breast cancer. In this study, we detected overexpression of the HOXB13 gene in endometrial cancer cells and tissues from patients by quantitative real-time RT-PCR. 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. We revealed that the invasive ability of antisense-transfectants showed a 90% reduction compared with parental cells and control transfectants (p<0.01). In addition, administration of 17beta-estradiol induced time- and dose-dependent responses of the HOXB13 expression in endometrial cancer AN3CA cells. These results suggest that overexpression of HOXB13 in endometrial cancer may be associated with the invasive ability of cancer cells with regulation by estrogen.

HOXB13 Induces Growth Suppression of Prostate Cancer Cells as a Repressor of Hormone-Activated Androgen Receptor Signaling

Androgen receptor (AR) signals play a decisive role in regulating the growth and differentiation of both normal and cancerous prostate cells by triggering the regulation of target genes, in a process in which AR cofactors have critical functions. Because of the highly prostate-specific expression pattern of HOXB13, we studied the role of this homeodomain protein in prostate cells. Expression of HOXB13 was limited to AR-expressing prostate cells. Reporter transcription assay demonstrated that HOXB13 significantly suppressed hormone-mediated AR activity in a dose-responsive manner, and suppression was specific to AR with which HOXB13 physically interacts. Overexpression of HOXB13 further down-regulated the androgen-stimulated expression of prostate-specific antigen, and suppression of endogenous HOXB13 stimulated transactivation of AR. Functionally, HOXB13 suppressed growth of LNCaP prostate cancer cells, which could be counteracted by additional hormone-activated AR. On the other hand, the growth-suppressive function of HOXB13 in AR-negative CV-1 cells was not affected by AR. These results suggest that HOXB13 functions as an AR repressor to modulate the complex AR signaling and subsequent growth regulation of prostate cancer cells. In addition to the loss of HOXB13 expression, maintaining AR may be an important step for prostate cancer cells to tolerate the suppressor function of HOXB13. Altogether, our data present a novel mechanism for the HOXB13-mediated repression of AR signaling, which can be interpreted to a growth-suppressive event.