The adenovirus E1A oncoprotein renders primary cells sensitive to the induction of apoptosis by diverse stimuli, including many anticancer agents. E1A-expressing cells accumulate p53 protein, and p53 potentiates drug-induced apoptosis. To determine how E1A promotes chemosensitivity, a series of E1A mutants were introduced into primary human and mouse fibroblasts using high-titer recombinant ret...

The aberrant expression of DNA methyltransferases (DNMTs) has been considered to be associated with pancreatic carcinogenesis and progression. DNMT3a is widely involved in cell proliferation and cell cycle progression in pancreatic ductal adenocarcinoma (PDAC) cells. However, its regulation of chemosensitivity to gemcitabine (GEM) and oxaliplatin (OXA) in p53‑deficient PDAC remains unclear. In ...

Decreased expression of E-cadherin correlates with poor prognosis in colorectal cancer. Certain E-cadherin signaling cascades are triggered by intercellular force or binding to cadherins on adjacent cells. Three-dimensional (3D) cell cultures represent a better approximation of cell-cell adhesion in vivo than two-dimensional (2D) cultures. Here, we explored the role of E-cadherin in colorectal ...

PURPOSE To identify biomarkers within the breast cancer genome that may predict chemosensitivity in breast cancer. EXPERIMENTAL DESIGN We conducted an RNA interference (RNAi) screen within the breast cancer genome for genes whose loss-of-function enhanced docetaxel chemosensitivity in an estrogen receptor-negative, progesterone receptor-negative, and Her2-negative (ER-, PR-, and Her2-, respec...

BACKGROUND In a previous analysis using a lung cancer cell line model, we have found that therapies directed against secreted clusterin (sCLU) and its downstream signaling targets pAkt and pERK1/2 may have the potential to enhance the efficacy of cisplatin (DDP)-based chemotherapy in vitro. Here, we investigated the therapies directed against sCLU on the DDP-based chemotherapy in vivo and explo...

OBJECTIVES In a previous analysis using a lung cancer cell lines model, we have found that therapies directed against sCLU and its downstream signaling targets pAkt and pERK1/2 may have the potential to enhance the efficacy of cisplatin (DDP)-based chemotherapy in vitro. Here, we investigated the therapies directed against sCLU on the DDP-based chemotherapy in vivo, and explored the mechanism. ...

Cancer chemotherapeutic drugs induce apoptosis by several pathways. Inactivation of proapoptotic genes, or activation of survival signaling, leads to chemoresistance. Activator protein 2alpha (AP-2alpha), a developmentally regulated sequence-specific DNA-binding transcription factor, has been shown to function like a tumor suppressor. Here, we show that controlled expression of AP-2alpha, using...

Folylpolyglutamyl synthase (FPGS) converts intracellular folates and antifolates to polyglutamates. Polyglutamylated folates and antifolates are retained in cells longer and are better substrates than their monoglutamate counterparts for enzymes involved in one-carbon transfer. FPGS modulation affects the chemosensitivity of cancer cells to antifolates, such as methotrexate, and 5-fluorouracil ...