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Date:6/13/2011

then tested the cell lines to see how much calcium it would take for the receptors on those cells to produce the maximum amount of the PTHrP hormone. All three lines produced the highest hormone levels when the calcium concentration reached the equivalent of 12 milligrams per deciliter of calcium in blood in humans the level at which hypercalcemia is diagnosed. Normal values range from 8.5 to 10.2 milligrams per deciliter.

"This told us that when people are hypercalcemic, they are producing the maximum level of PTHrP," Lorch said.

An experiment in mice confirmed the calcium-sensing receptor's role. Mice were injected with either regular tumor cells or cells from which the calcium-sensing receptor had been stripped away. Mice that received cells without the receptor developed hypercalcemia in 49 days, compared to 29 days for mice that received typical tumor cells, which do have the receptor.

"That's a very big difference in time in mice," Lorch said. "This suggests that the calcium-sensing receptor was necessary for the rapid development of hypercalcemia."

The receptors on those cells also behaved as expected in additional cell line experiments exploring their behavior after the PTHrP hormone was released. All three lines led to the release of what is known as intercellular calcium, but at different levels and rates. One line in particular stood out. This line, called HARA, had previously produced the most PTHrP when stimulated with calcium, and then released much more excess calcium than the other two cell lines.

These findings in the tissue studies led the scientists to sequence the calcium-sensing receptors in the three cell lines to look for genetic variants. The HARA line contained a mutation known as a single nucleotide polymorphism, or SNP (pronounced snip), that influenced how much of the PTHrP protein the receptors produced and how much calcium it took to stimulate that action.

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Contact: Gwendolen Lorch
gwendolen.lorch@cvm.osu.edu
614-292-9698
Ohio State University
Source:Eurekalert

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