hikichi masahiro

A 50-year-old woman with a large right breast mass was emergently hospitalized for generalized weakness and fatigue. A histological examination of tumor biopsy specimens revealed a phyllodes tumor (PT). She suddenly lost consciousness due to severe hypoglycemia. Non-islet cell tumor hypoglycemia (NICTH) due to the PT was suspected. The tumor was emergently resected. A histological examination revealed a borderline PT. The patient recovered from the hypoglycemic episode. High-molecular-weight insulin-like growth factor II was detected in serum that had been collected preoperatively and in the tumor tissue, but not in serum that had been collected postoperatively. We herein present a case of a borderline PT with NICTH.

Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)alpha-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ER alpha serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ER alpha phosphorylation at Ser167. The tumor suppressor serine/threonine-protein phosphatase 2A (PP2A) regulates the phosphatidylinositol 3-kinase/RAC serine/threonine-protein kinase signaling pathway. A previous study indicated that PP2A inhibition decreased ER alpha Ser167 phosphorylation and estradiol (E-2)-independent cell growth. The present study investigated the potential relevance of PP2A in E-2 deprivation-resistant MCF-7 cells. E-2 depletion reduced the susceptibility of MCF-7 cells to inhibitors of mechanistic target of rapamycin (mTOR) and significantly increased ER alpha Ser167 phosphorylation and decreased expression of PP2A. Conversely, long-term E2-deprived (LTED) MCF-7 cells, a model of AI-resistant breast cancer, exhibited decreased ERa Ser167 phosphorylation and further upregulation of PP2A in E-2-containing medium. The PP2A activator forskolin (FSK) significantly inhibited LTED cell proliferation by increasing the effect of everolimus (Eve), an mTOR inhibitor. In summary, the present study provides further evidence that PP2A represents a therapeutic target for AI-resistant breast cancer.