Dual Signals from Gene Promote Breast Cancer Growth

Researchers studying how cancer cells spread within the hollow spaces or lumen of the human breast have found that two separate genetic signals are required to prevent cell death and allow proliferation, and that the common breast cancer gene, HER2 (also called ErbB2), is able to provide both signals. Their findings were published in the October 4, 2002, issue of Cell.

The investigators, from Harvard Medical School (Boston, MA, USA), utilized an in vitro three-dimensional epithelial cell culture model to analyze the role of apoptosis in the formation and maintenance of a hollow glandular architecture.

They found that neither inhibiting apoptosis (by exogenously expressing antiapoptotic Bcl family proteins) nor enhancing proliferation (via Cyclin D1 or HPV E7 overexpression) caused luminal filling, suggesting that the glandular architecture was able to resist such isolated oncogenic insults. However, the lumen became filled when oncogenes that enhance proliferation were co-expressed with those that inhibit apoptosis, or when ErbB2, which induces both activities, was activated by homodimerization.

These studies showed that during the early development of breast cancer, tumor cells must not only proliferate but also overcome the normal cell death mechanisms that maintain the glandular architecture.



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