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Berkeley Lab researchers illuminate laminin's role in cancer formation
Date:3/7/2011

ral fellow, Virginia Spencer, in Berkeley Lab's Life Sciences Division, have now shown that the addition of laminin-111 leads to quiescence in breast epithelial cells through changes in nuclear actin.

"We found that high levels of laminin-111 depleted nuclear actin and this in turn induced cell quiescence," Bissell says. "Furthermore, this process can be prevented if a form of actin that can not exit the nucleus is introduced. Under these conditions the cells do not stop growing even in the presence of laminin."

In their study, Bissell and Spencer and their colleagues used a unique three-dimensional cell culture assay developed by Bissell's research group, and worked with mouse and human mammary epithelial cells. Through the addition of laminin-111, they were able to decrease nuclear actin levels in the cultured cells, which reduced DNA synthesis and transcription. When nuclear actin levels were deliberately over-expressed, the effects were reversed and cells were prevented from becoming quiescent even in the presence of laminin-111. Furthermore, the high levels of nuclear actin were concentrated in regions of the breast cells where there was little or no laminin-111. Taken together, the results implicate laminin-111 as the regulator of nuclear actin and nuclear actin as a key mediator of epithelial cell quiescence.

"In collaboration with Ole Petersen's laboratory, we had found previously that the ECM surrounding tissues from breast cancers has a dramatic reduction in laminin-111 in comparison to the ECM surrounding a normal breast cell, which is rich in laminin-111," Bissell says. "However, just giving laminin back to cancer cells was not enough to make them normal so other factors are clearly also involved and one such factor we now know is how laminin-111 and nuclear actin talk to each other!"

Says Spencer, "Ours is the first study to actually identify laminin-111 as the physiological regulator of nuclear actin and to
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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