Cigarette smoke induces nuclear translocation of heme oxygenase 1 (HO-1) in prostate cancer cells: nuclear HO-1 promotes vascular endothelial growth factor secretion.

Prostate cancer is the second leading cause of male-cancer related death in the United States. Despite a number of evidence-based studies which strongly suggest an association between cigarette smoking and prostate cancer, the underlying biological mechanism is largely unknown. Heme oxygenase 1 (HO-1) has been implicated in maintaining cellular homeostasis, but also in tumor angiogenesis.

Wild-type BRCA1, but not mutated BRCA1, regulates the expression of the nuclear form of beta-catenin.

BRCA1 is an essential caretaker protein in the surveillance of DNA damage, is mutated in approximately 50% of all hereditary breast cancer cases, and its expression is frequently decreased in sporadic breast cancer. beta-Catenin is a multifunctional protein that forms adhesion complex with E-cadherins, alpha-catenin, and actin, and plays a central role in Wnt signaling through its nuclear translocation and activation of beta-catenin-responsive genes. Although significant progress has been made in understanding the Wnt/beta-catenin and BRCA1 signaling cascades, it is not known whether there is a link between beta-catenin and BRCA1.

BRCA1 interacts with Smad3 and regulates Smad3-mediated TGF-beta signaling during oxidative stress responses.

Background: BRCA1 is a key regulatory protein participating in cell cycle checkpoint and DNA damage repair networks. BRCA1 plays important roles in protecting numerous cellular processes in response to cell damaging signals. Transforming growth factor-beta (TGF-beta) is a potent regulator of growth, apoptosis and invasiveness of tumor cells.

The nuclear matrix protein, NRP/B, enhances Nrf2-mediated oxidative stress responses in breast cancer cells.

The transcription factor NF-E2-related factor 2 (Nrf2) translocates into the nucleus and activates phase II genes encoding detoxification enzymes and antioxidant proteins, resulting in the protection of cells from oxidative insults. However, the involvement of Nrf2-mediated oxidative stress responses in breast cancer cells is largely unknown. Notably, during our study of the Nrf2 pathway in breast cancer cells, we observed that the nuclear matrix protein NRP/B was expressed and colocalized with Nrf2 in these cells, suggesting that NRP/B is involved in Nrf2-mediated oxidative stress responses.

Integrin regulation by vascular endothelial growth factor in human brain microvascular endothelial cells: role of alpha6beta1 integrin in angiogenesis.

The precise role of vascular endothelial growth factor (VEGF) in regulating integrins in brain microvascular endothelial cells is unknown. Here, we analyzed VEGF effects on integrin expression and activation in human brain microvascular endothelial cells (HBMECs). Using human cDNA arrays and ribonuclease (RNase) protection assays, we observed that VEGF up-regulated the mRNA expression of alpha(6) integrin in HBMECs.

RAFTK/Pyk2 regulates EGF-induced PC12 cell spreading and movement.

The protein tyrosine kinase RAFTK, also termed Pyk2, is a member of the focal adhesion kinase (FAK) subfamily. In this report, we show the role of RAFTK in neuroendocrine PC12 cells upon epidermal growth factor (EGF) stimulation. Following EGF treatment, we observed that RAFTK was tyrosine-phosphorylated in a time- and dose-dependent manner, while FAK was constitutively phosphorylated and primarily regulated by cell adhesion.

Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha.

The interaction between 17beta-estradiol and estrogen receptor alpha (ER-alpha) plays an important role in breast carcinogenesis and breast cancer treatment. ER-alpha is a critical growth regulatory gene in breast cancer and its expression level is tightly linked to the prognosis and treatment outcomes of breast cancer patients. Loss of ER-alpha expression in breast epithelial cells is critical for breast cancer progression.

Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells.

Mutational inactivation of BRCA1 confers increased risk for breast cancer. However, the underlying basis for the breast tissue-restricted, tumor-suppressive properties of BRCA1 remains poorly defined. Here, we show that BRCA1 and the estrogen receptor alpha (ER-alpha) modulated vascular endothelial growth factor (VEGF) gene transcription and secretion in breast cancer cells.

A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer.

Germ-line mutations in BRCA1 predispose individuals to breast and ovarian cancers. We observed a novel endogenous association of BRCA1 with Nmi (N-Myc-interacting protein) in breast cancer cells. Nmi was found to interact specifically with BRCA1, both in vitro and in vivo, by binding to two major domains in BRCA1, amino acid residues 298-683 and 1301-1863.