Modulation of telomeres in alternative lengthening of telomeres type I like human cells by the expression of werner protein and telomerase.

The alternative lengthening of telomeres (ALT) is a recombination-based mechanism of telomere maintenance activated in 5-20% of human cancers. In Saccharomyces cerevisiae, survivors that arise after inactivation of telomerase can be classified as type I or type II ALT. In type I, telomeres have a tandem array structure, with each subunit consisting of a subtelomeric Y' element and short telomere sequence.

Omega-3 fatty acid inhibition of prostate cancer progression to hormone independence is associated with suppression of mTOR signaling and androgen receptor expression.

Currently, progression of prostate cancer to androgen independence remains the primary obstacle to improved survival. In order to improve overall survival, novel treatment strategies that are based upon specific molecular mechanisms that prolong the androgen-dependent state and that are useful for androgen-independent disease need to be identified. Both epidemiological as well as preclinical data suggest that omega-3 fatty acids are effective primary tumor prevention agents; however, their efficacy at preventing and treating refractory prostate cancer has not been as thoroughly investigated.

Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins Survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways.

Background: The oncoprotein HER-2 is over-expressed and/or has undergone gene amplification in between 20 to 30% of breast and ovarian cancers. HER-2 amplified breast cancer is associated with a poor prognosis and increased resistance to chemo- and hormonal therapy. Data supporting the transforming potential of HER-2 are irrefutable but the mechanism by which HER-2 contributes to this process is complex and a unified model of HER2-induced increased cell proliferation and survival has not emerged.

Akt-induced tamoxifen resistance is associated with altered FKHR regulation.

The Akt kinase is a serine/threonine protein kinase that has been implicated in mediating a variety of biological responses, is associated with a poor pathophenotype in breast carcinoma, and is involved in hormone and chemotherapy resistance, including resistance to the antiestrogen, tamoxifen. Akt promotes cell survival by phosphorylating and inactivating proapoptotic proteins and increasing the transcription of survival genes. To explore the role that specific components of the Akt kinase pathway play in the cellular response to tamoxifen, we transfected MCF-7 cells with an expression plasmid for a constitutively active Akt.

Targeting telomerase.

Given the constitutive expression of telomerase in the majority of human tumors, telomerase inhibition is an attractive, broad-spectrum therapeutic target for cancer treatment. Therapeutic strategies for inhibiting telomerase activity have included both targeting components of telomerase (the protein component, TERT, or the RNA component, TERC) or by directly targeting telomere DNA structures. Recently a combination telomerase inhibition therapy has been studied also.

Dual luciferase assay system for rapid assessment of gene expression in Saccharomyces cerevisiae.

A new reporter system has been developed for quantifying gene expression in the yeast Saccharomyces cerevisiae. The system relies on two different reporter genes, Renilla and firefly luciferase, to evaluate regulated gene expression. The gene encoding Renilla luciferase is fused to a constitutive promoter (PGK1 or SPT15) and integrated into the yeast genome at the CAN1 locus as a control for normalizing the assay.

A novel telomere structure in a human alternative lengthening of telomeres cell line.

Cancer cells require mechanisms to maintain telomeres. Most use telomerase, but 5% to 20% of tumors use alternative lengthening of telomeres (ALT), a telomerase-independent mechanism that seems to depend on recombination. ALT is characterized by amplification of telomere TTAGGG repeats to lengths beyond 50 kb, by elevated rates of telomere recombination, and by nuclear structures called ALT-associated promyelocytic leukemia bodies.

Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Breast cancer cells are generally resistant to induction of apoptosis by treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we demonstrate that both TRAIL-sensitive and TRAIL-resistant breast cancer cell lines can be efficiently killed by overexpression of the TRAIL receptor, death receptor 4 (DR4). The extent of cell death depended on the strength of the promoter driving DR4 expression.