A protein located on the membrane of a cell's energy source can block the signal that tells cells to die, according to a study by researchers at The University of Texas (UT) Southwestern Medical Center at
A protein located on the membrane of a cell's energy source can blockthe signal that tells cells to die, according to a study by researchersat The University of Texas (UT) Southwestern Medical Center at Dallas.Discovery of the role of this protein in allowing cells to continue tomultiply into tumors instead of breaking down in a normal manner couldlead to more efficient cancer-fighting drugs.
Researchers found that BCL2, an integral protein on the outer membraneof mitochondria, a cell's principal energy source, prevents the releaseof an electron-carrier protein from the mitochondria. In healthy cells,an outflow of energy signals the beginning of apoptosis, or programmedcell death.
"We found that during apoptosis, the signal that comes out of mitochondriais a release of cytochrome c," said Xiaodong Wang, assistant professorof biochemistry at UT Southwestern and senior researcher on the study."Cytochrome c is a small soluble protein that triggers the cell deathprogram when it's released from the mitochondria."
Wang said his research team, which reported its findings in the February21st issue of Science, discovered that an overabundance of BCL2 stops therelease of cytochrome c, a carrier in the cell's energy chain.
Previously, scientists knew that BCL2 was a cancer-causing gene, butthey didn't know why the protein allowed tumor growth. They also knew thatcytochrme c was necessary for cell death to begin, but no one had foundthe connection between the two.
Using drugs administered in human chemotherapy treatment on cells invitro, Wang and his team found that cells undergoing apoptosis had an elevationof cytochrome c outside the mitochondria. When they introduced an elevatedamount of BCL2, cytochrome c was blocked from coming out of the mitochondria.Therefore, cell death did not begin.
Overabundance of BCL2 May Cause Resistance to Chemotherapy
Wang said one reason he took this approach in studying why cells donot die is that people going through chemotherapy build up a resistanceto the cancer-fighting drugs because they have an overabundance of BCL2.
"By finding exactly how the BCL2 works, we might be able to finda way to bypass this problem," he said. "Theoretically this couldbe important for cancer treatment because someone might be able to finda drug that specifically targets the mitochondria."
The researchers now want to determine whether there are specific channelson the mitochondria membrane that control this cell activity and how theBCL2 protein influences these channels. They also want to figure out themechanism by which BCL2 blocks the release of protein from mitochondria.
"It's very satisfactory for us to finally understand why a proteinon the mitochondria can prevent cell death," Wang said. The otherscientists involved in the study were UT Southwestern researcher Xue-songLiu and Emory University researchers Jie Yang, Kail Bhalla, Caryn NaekyungKim, Ana Maria Ibrado, Jiyang Cai, Tsung-I Peng, and Dean P. Jones.
The study was partially funded by an American Cancer Society researchgrant.