Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer

Abstract

The androgen receptor (AR) plays a critical role in the development and the progression of prostate cancer. Alterations in the expression of AR coregulators lead to AR hypersensitivity, which is one of the mechanisms underlying the progression of prostate cancer into a castrate-resistant state. Octamer transcription factor 1 (Oct1) is a ubiquitous member of the POUhomeodomain family that functions as a coregulator of AR. In our study, the contribution of Oct1 to prostate cancer development was examined. Immunocytochemistry analysis showed that Oct1 is expressed in the nuclei of LNCaP cells. siRNA-mediated silencing of Oct1 expression inhibited LNCaP cell proliferation. Immunohistochemical analysis of Oct1 expression in tumor specimens obtained from 102 patients with prostate cancer showed a positive correlation of Oct1 immunoreactivity with a high Gleason score and AR immunoreactivity (p 5 0.0042 and p < 0.0001, respectively). Moreover, patients with high immunoreactivity of Oct1 showed a low cancer-specific survival rate, and those patients with high immunoreactivities of both Oct1 and AR exhibited poorer cancer-specific prognosis. Multivariate hazard analysis revealed a significant correlation between high Oct1 immunoreactivity and poor cancer-specific survival (p 5 0.012). These results demonstrate that Oct1 can be a prognostic factor in prostate cancer as a coregulator of AR and may lead to the development of a new therapeutic intervention for prostate cancer.The androgen receptor (AR) plays a critical role in the progression of prostate cancer.1 AR is a member of the nuclear receptor superfamily and functions as a ligand-dependent transcription factor.2 Upon activation by androgens, AR translocates into the nucleus and binds to the androgen responsive elements (AREs). The transactivation of AR involves several coregulatory proteins. AR coregulators are proteins that interact with AR to enhance (coactivators) or reduce (corepressors) transactivation of target.

Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer

“…It has been known that CSC characteristics may lead to cancer aggressiveness, chemoresistance to anticancer drugs, and a high risk of recurrence in patients with cancer (29,31,32,43). Recent reports suggest that tumorigenicity and tumor progression is driven by CSC characteristics, and CSCs consistently showed elevated EZH2 and SUZ12 expression (24)(25)(26)(27)(28).…”

Expression of Androgen and Estrogen Signaling Components and Stem Cell Markers to Predict Cancer Progression and Cancer-Specific Survival in Patients with Metastatic Prostate Cancer

“…Therefore, measurement of the expression of selected AR downstream targets can provide information on the individual functional status of ARs in prostate cancer cells. We previously defined an AR transcriptional network in prostate cancer cells using ChIP-chip and CAGE assays (18) and also analyzed the AR-related genes APP, Oct1, and FOXP1 in prostate cancer (7,11,12). In these experiments, APP and Oct1 were correlated with prostate cancer aggressiveness and both were considered therapeutic targets (7,12).…”

“…We previously defined an AR transcriptional network in prostate cancer cells using ChIP-chip and CAGE assays (18) and also analyzed the AR-related genes APP, Oct1, and FOXP1 in prostate cancer (7,11,12). In these experiments, APP and Oct1 were correlated with prostate cancer aggressiveness and both were considered therapeutic targets (7,12). Some FOX proteins that are involved in cell growth and differentiation as well as in embryogenesis and longevity are known to be AR-related genes (8).…”

“…Immunohistochemical analysis for AR and Klf4 was performed with the streptavidin-biotin amplification method using an EnVisionþ Visualization Kit (Dako) for AR and Klf4, as previously described (12,26). The primary antibody against AR and Klf4 (1:50 dilution) was applied and incubated at room temperature for 1 hour.…”

“…7), forkhead-box (FOX) family proteins (8)(9)(10)(11), octameter transcription factor (Oct1; ref. 12), and ERs (5,13,14). However, the distribution and functions of these steroid nuclear receptors vary depending on the sites from which prostate cancer samples are obtained (13)(14)(15).…”