Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC(1638N/+) Mice.

Purpose: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation.

Methods And Materials: Male and female APC(1638N/+) mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, (12)C, (28)Si, or (56)Fe radiation.

Wip1 abrogation decreases intestinal tumor frequency in APC(Min/+) mice irrespective of radiation quality.

Low-linear energy transfer (low-LET) γ-ray exposure is a risk factor for colorectal cancer (CRC). Due to their high-LET nature, energetic iron ions found in space are expected to pose greater CRC risks to astronauts undertaking long-duration space missions beyond low Earth orbit. Wild-type p53-induced phosphatase 1 (Wip1) is important for cellular DNA damage response and its abrogation has been shown to inhibit spontaneous intestinal tumorigenesis in APC(Min/+) mice, a well-studied mouse model of human CRC.

ERK/MAPK regulates ERRγ expression, transcriptional activity and receptor-mediated tamoxifen resistance in ER+ breast cancer.

Selective estrogen receptor modulators such as tamoxifen (TAM) significantly improve breast cancer-specific survival for women with estrogen receptor-positive (ER+) disease. However, resistance to TAM remains a major clinical problem. The resistant phenotype is usually not driven by loss or mutation of the estrogen receptor; instead, changes in multiple proliferative and/or survival pathways over-ride the inhibitory effects of TAM.

Identification of an anchor residue for CheA-CheY interactions in the chemotaxis system of Escherichia coli.

Transfer of a phosphoryl group from autophosphorylated CheA (P-CheA) to CheY is an important step in the bacterial chemotaxis signal transduction pathway. This reaction involves CheY (i) binding to the P2 domain of P-CheA and then (ii) acquiring the phosphoryl group from the P1 domain. Crystal structures indicated numerous side chain interactions at the CheY-P2 binding interface.