HER2 and cancer
Amplification or over-expression of the ERBB2 gene occurs in approximately 15-30% of breast cancers. It is strongly associated with increased disease recurrence and a poor prognosis. Over-expression is also known to occur in ovarian, stomach, and aggressive forms of uterine cancer, such as uterine serous endometrial carcinoma.
Aurora A dysregulation has been associated with high occurrence of cancer. For example, one study showed over-expression of Aurora A in 94 percent of the invasive tissue growth in breast cancer, while surrounding, healthy tissues had normal levels of Aurora A expression. Aurora A has also been shown to be involved in the Epithelial–mesenchymal transition and Neuroendocrine Transdifferentiation of Prostate Cancer cells in aggressive disease.
Dysregulation of Aurora A may lead to cancer because Aurora A is required for the completion of cytokinesis. If the cell begins mitosis, duplicates its DNA, but is then not able to divide into two separate cells it becomes an aneuploid- containing more chromosomes than normal. Aneuploidy is a trait of many cancerous tumors. Ordinarily, Aurora A expression levels are kept in check by the tumor suppressor protein p53.
Mutations of the chromosome region that contains Aurora A, 20q13, are generally considered to have a poor prognosis.
Can’t find any information as it relates to cancer. The closest I get is this:
Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit (Gs-α), a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular responses. Multiple transcript variants have been found for this gene, but the full-length nature and/or biological validity of some variants have not been determined.
Deficiencies are associated with:
Albright hereditary osteodystrophy
pseudohypoparathyroidism type Ia – Thought this was interesting since I have no working thyroid
pseudohypoparathyroidism type Ib
Mutations in this gene also result in progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors.
p53 has many mechanisms of anticancer function, and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works through several mechanisms:
It can activate DNA repair proteins when DNA has sustained damage. Thus, it may be an important factor in aging.[
It can arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle).
It can initiate apoptosis – programmed cell death – if DNA damage proves to be irreparable.
p53 pathway: In a normal cell p53 is inactivated by its negative regulator, mdm2. Upon DNA damage or other stresses, various pathways will lead to the dissociation of the p53 and mdm2 complex. Once activated, p53 will induce a cell cycle arrest to allow either repair and survival of the cell or apoptosis to discard the damaged cell. How p53 makes this choice is currently unknown.
Activated p53 binds DNA and activates expression of several genes including microRNA miR-34a, WAF1/CIP1 encoding for p21 and hundreds of other down-stream genes. p21 (WAF1) binds to the G1-S/CDK (CDK4/CDK6, CDK2, and CDK1) complexes (molecules important for the G1/S transition in the cell cycle) inhibiting their activity.
When p21(WAF1) is complexed with CDK2 the cell cannot continue to the next stage of cell division. A mutant p53 will no longer bind DNA in an effective way, and, as a consequence, the p21 protein will not be available to act as the “stop signal” for cell division] – THIS COMBINED WITH THE HER2 CELL DIVISION ACCELLERATION SOUNDS LIKE A BAD COMBINATION
The protein encoded by this gene is a membrane-associated GTP-ase and localizes to the plasma membrane. It is related to the ADP-ribosylation factor (ARF) and ARF-like (ARL) genes. The gene is located in a gene cluster that includes the a gene (M68) that is overexpressed in some tumors.
Chromosomal segregation during mitosis as well as meiosis is regulated by kinases and phosphatases. The Aurora kinases associate with microtubules during chromosome movement and segregation. Aurora kinase B localizes to microtubules near kinetochores, specifically to the specialized microtubules called K-fibers, and Aurora kinase A (MIM 603072) localizes to centrosomes (Lampson et al., 2004).[supplied by OMIM]
In cancerous cells, over-expression of these enzymes causes unequal distribution of genetic information, creating aneuploid cells, a hallmark of cancer.
Mutations in the gene have been linked with pancreatic agenesis and congenital heart defects