Hypoxia is a common feature of most tumors and is a product of rapid cell growth and poor vascularization1. When oxygen availability is low in the tumor environment, the hypoxia inducing transcription factors (HIFs) regulate a variety of signaling programs that can affect the balance between tumor cell apoptosis2 and autophagy3. In normoxia, HIFs are bound by the von Hippel-Lindau protein (VHL) in the cytosol where it is degraded by the proteasome, however, under hypoxia HIFs are translocated to the nucleus where they activate survival signals.
September is Ovarian Cancer Awareness month and brings to focus a cancer that is estimated to be diagnosed in over 21,000 women in the US in 2014 (1). Ovarian cancer often goes undiagnosed due to the lack of symptoms until it metastasized into the pelvic or abdominal areas. Treatment typically requires surgery and chemotherapy.
Breast cancer 1, early onset (BRCA1) is a well-known tumor suppressor gene that was originally discovered due to its link with early-onset breast and ovarian cancer in women. The BRCA1 protein contains the following domains: RING finger, RAD51-interaction, and BRCT (BRCA1 C-terminus). The N-terminus RING domain enables binding to several proteins - including BARD1 (BRCA1-associated RING domain protein) - allowing the formation of heterodimers. The RING finger is important for tumor suppressor activity. The RAD51-interaction domain is involved in DNA double-stranded break (DSB) repair.
p73 has been identified as a long-lost cousin of the p53 tumor suppressor protein. It has high homology with both p53 and with p63, a gene implicated in the maintenance of epithelial stem cells. The presence of significant homology between the DNA-binding domains of p53, p63, and p73 suggest that they have overlapping functions. Targeted disruption of p73 leads to defects hippocampal dysgenesis, hydrocephalus, chronic inflammation, and infections.
Prostate cancer is caused by malignant cells developing in prostate tissue. Common warning signs of prostate cancer include problems with urination (sudden urges, pain, blood in urine, difficulty urinating), experiencing pain in the back and pelvis, and feeling tired/dizzy. There are different tests utilized to diagnose prostate cancer including PSA screening, TRUS, DRE, and biopsy.
Breast cancer is caused by malignant cells developing in breast tissue. It is the most commonly diagnosed cancer in women, but advancements in treatment options have seen the death rate decline since the 1990s. Common warning signs of breast cancer include lumps, changes in breast size or shape, discoloration, dimpling of the skin, new concentrated pain in the breast, and rash on the nipple. Yearly mammograms and self-exams are an important part of early detection of breast cancer.
Myc genes (L-Myc, N-Myc and C-Myc) are a family of transcription factors. c-Myc is involved in transcription regulation, apoptosis and cell growth. Mutations in c-Myc have been tied to several cancers.
Ataxia Telangiectasia Mutated (ATM) is a serine/threonine protein kinase that is the master regulator of the DNA double-strand break (DSB) repair pathway. ATM is a key part of the cell cycle machinery that activates checkpoint signaling in response to DSBs, apoptosis, and genotoxic insults. ATM normally exists in its inactive state as a dimer or tetramer - upon DNA damage, it dissociates into monomers triggered by its own autophosphorylation.
Cytochrome Cis an electron carrier protein that localizes in mitochondrion intermembrane space and has been identified as one of the key signaling molecules of apoptosis or programmed cell death. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol.