Menin Enhances Androgen Receptor-Independent Proliferation and Migration of Prostate Cancer Cells.

The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.

Breast Cancer Statistics in Korea, 2018.

Breast cancer is the most common malignancy in Korean women, and its incidence continues to increase. The Korean Breast Cancer Society (KBCS) established a nationwide breast cancer database through its online enrollment program in 1996. This study aimed to analyze the clinical characteristics of breast cancer in Korea, and to assess the pattern of changes in breast cancer management in 2018. We analyzed the KBCS and Korea Central Cancer Registry (KCCR) databases in 2018. In 2018, 28,157 patients were newly diagnosed with breast cancer, of whom 4,510 had noninvasive breast cancer and 23,647 had invasive breast cancer. The age-standardized rate of breast cancer in 2018 was 79.0 per 100,000 women (65.6 invasive, 13.4 noninvasive). The median age of female patients diagnosed with breast cancer in 2018 was 52 years, and the incidence of breast cancer was the highest in the 40-49-years age group (9,432 patients, 33.6%). The proportion of patients with stage 0 and stage I breast cancer continued to increase, accounting for 63.8% of cases, and breast-conserving surgery was performed more often than mastectomy (66.2% vs. 33.0%). The most common subtypes of breast cancer were hormone receptor [HR]-positive and human epidermal growth factor receptor-2 (HER2)-negative types (65.9% of cases), while the HR-negative and HER2-positive types accounted for 9.2% of cases. According to the KCCR data, from 2014 to 2018, the 5-year relative survival rate of patients with breast cancer was 93.3%, which was 14.0% higher than that from 1993 to 1995 (79.3%). The clinical characteristics of breast cancer in Korea have been changing, and national databases can improve our understanding of the disease characteristics of Korean women. Therefore, updating the KBCS registry is important for the effective management of breast cancer in Korea.