Inhibition of Polarity Protein Gene Triggers Cancer-Like Changes in Cell Shape

Researchers have identified a gene linked to the mechanism that determines cell shape and have shown how its lack characterizes certain types of cancer cells.

Investigators from the University of Virginia (Charlottesville, USA) used a novel shRNA lentiviral system to manipulate gene expression in mouse mammary stem/progenitor cells. The shRNA specifically inhibited expression of the protease activated receptor 3 (PAR3) gene. This gene encodes a polarity protein that controls how cells acquire particular shapes, so that they have a top and a bottom.

Results published in the June 15, 2009, issue of the journal Genes & Development revealed that transplantation of Par3-depleted stem/progenitor cells into the mammary fat pad severely disrupted mammary development. The investigators identified a novel function for the atypical protein kinase C (aPKC)-binding domain of Par3 in restricting Par3 and aPKC to the apical region of mammary epithelia in vivo, and found that mammary morphogenesis was dependent on the ability of Par3 to directly bind aPKC.

These results revealed a new function for Par3 in the regulation of progenitor differentiation and epithelial morphogenesis in vivo and demonstrated for the first time an essential requirement for the Par3–aPKC interaction.

"A big problem in biology is that there are many thousands of genes. Testing the function of any one of them in a living organism, such as a mouse, has traditionally been slow and very expensive,” said senior author Dr. Ian Macara, professor of microbiology at the University of Virginia. "The new technology is hundreds of times cheaper and many times faster than traditional approaches. While we used it to study the function of a specific breast-developing gene, our method can be replicated in screening for genes that can suppress tumors or cause cancer.”

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