Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging.

Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli.

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health.

The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways.

Targeting the cancer initiating cell: the Achilles' heel of cancer.

We have isolated cell with the cancer initiating cell (CIC) phenotype from PC3 cells. The PC3/(CIC) cells are more resistant than the PC3/(BC) cells to chemotherapeutic drugs such as docetaxel which is used to treat prostate cancer. Thus these prostate CICs could lay dormant and persist even after chemotherapeutic drug treatment.

Microarray and pathway analysis reveals decreased CDC25A and increased CDC42 associated with slow growth of BCL2 overexpressing immortalized breast cell line.

Bcl-2 is an anti-apoptotic protein that is frequently overexpressed in cancer cells but its role in carcinogenesis is not clear. We are interested in how Bcl-2 expression affects non-cancerous breast cells and its role in the cell cycle. We prepared an MCF10A breast epithelial cell line that stably overexpressed Bcl-2.

Allelic variation and environmental lead exposure in urban children.

The advent of the Human Genome Project has allowed for increased understanding and sophistication in diagnosis, treatment methods, and overall care planning on the part of healthcare providers for children with genetic disorders. Genetics research dealing with polymorphic changes within a genome has opened the door to awareness of how dormant genetic alleles may become active when coupled with certain environmental insults. Such genetic aberrations may place a child at a higher risk for health disparities when exposed to environmental toxins.