Expressional Difference of RHEB, HDAC1, and WEE1 Proteins in the Stromal Tumors of the Breast and Their Significance in Tumorigenesis

BACKGROUND: Fibroadenoma (FA) and phyllodes tumor (PT) are stromal tumors of breast and are histologically similar. There are no established differences in tumorigenesis and oncogene expression among them. Ras homolog enriched in brain (RHEB) plays an important role in cell growth and cell-cycle control, histone deacetylase 1 (HDAC1) is an important factor in breast tumor progression and prognosis, and WEE1 homolog (WEE1) functions as a tumor suppressor. No studies on the expressional differences of these proteins in FA and PT have been reported to date. METHODS: The expression of these proteins in FA, PT, and normal breast was compared. We used 102 cases of FA and 25 cases of benign PT. RESULTS: In epithelial cells, the expression of RHEB, HDAC1, and WEE1 was lowest in PT, higher in FA, and most enhanced in normal breast. In addition, the expression of RHEB and HDAC1 was higher in the stromal cells of PT than in FA and normal breast. CONCLUSIONS: Both epithelial and stromal cells of FA and PT express these proteins, which indicates that epithelial cells play an important role in the development of stromal tumors. In addition, the expressional differences of these proteins may be associated with the tumorigenesis of breast stromal tumors.

Hypoxia induces Wee1 expression and attenuates hydrogen peroxide-induced endothelial damage in MS1 cells

In an oxygen-depleted environment, endothelial cells initiate an adaptive pattern of synthesis, which may enable them to survive hypoxic crises. Using high-resolution two-dimensional gel electrophoresis in conjunction with mass spectroscopy, we obtained a 24 differential display of proteins in the pancreatic endothelial cell line, MS-1, at four time points following induction of hypoxia. The induction of Wee1 under hypoxia was confirmed both at the mRNA and protein levels. The phosphorylation of cell division cycle 2, which is downstream of Wee1, was also increased after hypoxic exposure. In addition, pre-exposure to hypoxia attenuated a decrease in hydrogen peroxide-induced cell number. The induction of bax (a pro-apoptotic protein) and reduction of bcl (an anti-apoptotic protein) after hypoxia stimulus were also attenuated by hypoxic pre-exposure. Moreover, hydrogen peroxide-induced morphologic damage did not appear in the wild-type Wee1-expressing cells. Taken together, our results suggest that Wee1 may have important role in hypoxia-induced pathophysiological situations in endothelial cells.