Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
For full article and contact information, see Angew. Chem. Int. Ed. 2002, 41 (24), 4769 - 4773
A Flare for Cancer
Hope for early detection: Fluorescing
molecule exposes defects in anti-tumor gene
The earlier a cancer is detected, the higher the chances of recovery. The need for a fast, simple, and also inexpensive method for early detection is correspondingly urgent. A diagnostic procedure developed by a team of researchers working with Markus Sauer in Heidelberg could fulfill this need. The starting point is the gene p53, also called the "guardian of the genome", because it can keep healthy cells from turning into tumor cells. If a cell's DNA is damaged, the cell "reads" gene p53 more often. Protein p53, which is produced by the gene, inhibits cell division until the damage can be repaired, or - if it's irreparable - until the cell dies. This hinders the uncontrolled growth of degenerate cells. It is thus always dangerous when p53 has a defect and can no longer function as a watchdog.
"It has been shown that mutations in gene p53 occur in 60 to 80 % of all tumors," reports Sauer. The immune system reacts to the p53 proteins produced according to the flawed "instructions" by producing autoanitibodies against them. Says Sauer, "the appearance of p53 autoantibodies in blood serum is nearly 100 % indicative of a malignant tumor." As it turns out, the antibodies are particularly aimed at two specific, short segments at one end of the protein. This is where the researchers started off. They reproduced these sequences and added on a fluorescent dye. Both of the fluorescent probes made in this way bind to the p53 autoantibodies. The final touch is this: if no antibodies are near, the probes are present as loops, because their dye-end attaches itself to a structurally compatible amino acid at the other end of the probe. In this state, the dye cannot glow. If the probes couple to the antibodies however, the loop is broken and the dye starts to glow again when it is exposed to laser light. Modern, highly sensitive, fluorescence microscopic techniques make it possible to detect such individual "beacon molecules" in a tiny drop of blood within minutes.
"In comparison to previous detection methods for p53 autoantibodies, our technique is substantially faster and cheaper. We also expect fewer false-positive results, owing to the homogeneous test format. This opens new diagnostic pathways for the early detection of cancer and for monitoring the progress of antitumor therapies," states Sauer.