Nuclear Receptor DAX1 in Human Prostate Cancer: A Novel Independent Biological Modulator

Abstract

Abstract. The orphan nuclear receptor DAX1 (dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1; NR0B1) has been known for its various roles in human development, specifically sex determination and steroidogenesis. Its expression has been reported in endocrine and sex steroid-dependent neoplasms such as human adrenocortical, pituitary, endometrial, and ovarian tumors. Prostate cancer is also sex steroid-dependent tumor in which androgens play important roles in the pathogenesis and development via androgen receptor (AR). DAX1 is also reported to repress AR activity in human prostate cancer cell line (LNCaP) but its biological roles have remained unclear in the human prostate cancer. The aim of this study is to examine the expression of DAX1 in human prostate cancer using immunohistochemistry in order to evaluate its possible biological and/or clinical significance. In this study, we examined the DAX1 immunoreactivity in human prostate cancer obtained from surgery (n = 40), and correlated the findings with clinicopathological features of the patients. Twenty-one cases were defined as positive cases for DAX1 immunoreactivity (53%). Immunoreactivity for DAX1 was inversely and significantly correlated with Gleason score (P<0.05). However, DAX1 immunoreactivity was not significantly correlated with the status of sex steroid receptors we examined. DAX1 immunoreactivity is considered a new biological modulator of human prostate cancer, but independent to the status of sex steroid receptors in human prostate cancer tissues.

Tumorigenic Role of Orphan Nuclear Receptor NR0B1 in Lung Adenocarcinoma

“…26,28 Whereas, the subcellular localization of NR0B1 was various among cases with the present lung adenocarcinoma. Kawajiri et al 43 reported that NR0B1 localization changed during pituitary development from nucleocytoplasmic at embryonic day 10.5 to nucleus at day 18.5.…”

“…In contrast, the knocked-down expression of NR0B1 did not affect the cell proliferation of A549 cells. This might be attributable to the difference of cell types; Saito et al 26 and Nakamura et al 28 did not find any correlation of NR0B1 expression level with the Ki-67 labeling index, a well-established marker for cell proliferative activity, in the endometrial adenocarcinoma of uterus and prostate. The present study on the clinical cases of lung adenocarcinoma showed that NR0B1 expression level did not correlate with the size of tumors.…”

“…According to the method by Saito et al, 26 a total of more than 500 tumor cells from three different representative fields were examined, and the proportion of cells with NR0B1 signals was counted. The previous reports on NR0B1 expression in endometrial adenocarcinoma 26 and prostatic carcinoma 28 used a cut-off point of 10%. Therefore, in this study, we used the same cut-off point; the cases with more than 10% positive cells and fewer than 10% positive cells were defined as NR0B1-hi and NR0B1-lo, respectively.…”

WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

“…It is reported to be high in normal prostate epithelial cells but reduced in BPH (Holter et al 2002, Agoulnik et al 2003. Nuclear expression of DAX1 is also reported to be reduced with increasing Gleason grade (Nakamura et al 2009a). However, in the same report, normal tissue had no detectable DAX1 expression.…”

Role of Orphan Nuclear Receptor DAX-1/NR0B1 in Development, Physiology, and Disease

“…DAX-1 immunoreactivity correlated inversely with Gleason score, a grading system used to assess malignancy in this type of cancer [153].…”