Suppression of breast cancer cell growth by Her2-reduced AR serine 81 phosphorylation.

Breast cancer is a hormone-related carcinoma and the most commonly diagnosed malignancy in women. Although Her-2, estrogen receptor (ER), and progesterone receptor (PR) are the major diagnostic markers and therapeutic targets to breast cancer, searching for additional molecular targets remains an important issue and one of the candidates is androgen receptor (AR). AR has been shown expressed in 70% breast cancer patients and connects to low recurrence and high survival rate. Our previous study demonstrates that Ser81 phosphorylation of AR in prostate cancer cells is critical for its protein stability modulated by human epidermal growth factor receptor-2 (Her2). The aim of this study is to investigate the influence of Her2 and AR in proliferation of breast cancer cell line, MDA-MB-453. The data show that AR which was activated by synthetic androgen R1881 suppressed the proliferation of MDA-MB-453 cells. Notably, AR activation decreased the protein levels of cell growth-related proteins, including cyclin A, cyclin B, and early growth response protein 1 (Egr1), while cell-cycle inhibitor protein p27 was increased. Besides, Heregulin (HRG)-induced Her2 activation decreased the AR protein levels and its Ser81 phosphorylation. Her2 small molecular inhibitor, Lapatinib, dose-dependently suppressed cell proliferation while the levels of phospho-Ser81 AR and p27 protein were increased. Phospho-Ser81 AR was also increased after Her2 knockdown. Specifically, the influence of phospho-Ser81 AR by Lapatinib was primarily found in the nucleus of MDA-MD-453 cells, where the cell proliferation might directly be interfered. In conclusion, our findings indicate that Her2 might negatively regulate AR phosphorylation/activation and contribute to regulate the proliferation of MDA-MB 453 cells.

Diverse presentations in pediatric Meckel's diverticulum: a review of 100 cases.

BACKGROUND: Our objective was to analyze demographics and characteristics of Meckel's diverticulum with different manifestations in pediatric patients. METHODS: This is a retrospective study in children with symptomatic Meckel's diverticulum who underwent resection between September 1998 and October 2010. The diagnosis was confirmed by surgery and pathology. Demographic characteristics, manifestations, Meckel's scan results, surgical and histological findings were analyzed. RESULTS: One hundred symptomatic Meckel's diverticula were identified in 74 boys and 26 girls aged from one day to 18 years old over 13 years. Depending on whether or not obstruction occurred, the patients were classified into two categories. Each category was further subdivided into two diagnostic groups: 17 intussusception and 24 non-intussusception bowel obstruction in the obstructive category and 44 gastrointestinal bleeding and 15 diverticulitis and/or perforation in the non-obstructive category. The sex discrepancy was higher in the non-obstructive category than in the obstructive category (male-to-female, 4.36 vs. 1.73, p < 0.05). Forty-one of 44 patients with gastrointestinal bleeding underwent a Meckel's scan with a high positive rate (92.7%). The ectopic tissues were identified in 73 patients and included 61 gastric type, two pancreatic type and 10 mixed type. Ectopic tissues were more prevalent in non-obstructive category (p < 0.05) with ectopic gastric tissue even more pronounced (p < 0.01). Ectopic pancreatic tissue was significantly more prevalent in intussusception (p < 0.01). Laparoscopic surgery was performed more frequently in Meckel's diverticulum with non-obstructive symptoms (p < 0.001). CONCLUSION: Diverse presentations in pediatric Meckel's diverticulum are affected by different ectopic tissue types and male sex. Laparoscopic surgery is widely used for children with non-obstructive symptoms.