Dr Penna

A team of scientists at Cold Spring Harbor Laboratory has just published research identifying an enzyme called Brk that may serve as a target for future drugs developed to fight ErbB2-positive tumors. ErbB2 is a member of a family of enzymes called receptor tyrosine kinases — cell-surface molecules that goad cells into proliferating when they sense growth cues in the environs of cells that express them. It turns out that the over-production of ErbB2 in breast cancers is due to a gene mutation that results in the accumulation of multiple copies of the erbB2 gene.

Other genes that undergo such “amplification” due the duplication of DNA segments include brk, which is the gene that instructs cells to manufacture the enzyme Brk. This enzyme is absent in healthy cells but is found at high levels in a majority of breast cancers. As some of these cancers also over-express ErbB2, the CSHL team wondered whether the offending genes, erbB2 and brk, are mutated in tandem, or “co-amplified.” This idea in turn raised the possibility that the proteins encoded by these genes are also co-activated and feed into the same proliferation-promoting pathway.

Aside from hurrying along tumor progression, Brk was also found to diminish the effectiveness of ErbB2-inhibiting drugs on tumor growth. Brk-inhibitors might also be useful on their own or as combined with ErbB2 inhibiting drugs. The CSHL scientists speculate that these drugs might fight tumors that never react to or become resistant to ErbB2-inhibitors.

The newly discovered gene called calcium homeostasis modulator 1 (CALHM1), protein produced from the gene acts as Calcium channel. Research evidence shows that different variants of the gene also influence the levels of amyloid-ß peptides. The risk gene leads to a partial loss of function, which means that less calcium gets into the cell and it weakens the signals normally regulated by calcium. The researchers determined that one of these signals controls the levels of amyloid peptides, the building blocks of the characteristic senile plaques.

Researchers at The Feinstein Institute for Medical Research and Albert Einstein College of Medicine found, a variant of CALHM1 is found more frequently in people with Alzheimer’s disease than in those without. They estimate that a single copy of that variant, which results in a proline-to-leucine amino acid substitution (designated as p86L because it occurs at codon 86), increases one’s chance of getting late-onset Alzheimer’s disease by 1.44-fold.

Other genitic risk factors identified for late-onset Alzheimer’s is Apo-E4. Just one copy of this gene variant triples the risk of the disease.