Dual Gene Activation Characterizes Breast Tumors

Cancer researchers have shown that the uPAR gene is overexpressed primarily in the same breast cancer cells that overexpress another cancer gene, HER-2, adding another potential target for chemotherapeutic attack.

uPAR is a component of the plasminogen activation system, which in the healthy body is involved in tissue reorganization events such as mammary gland involution and wound healing. In order to be able to reorganize tissue, it is necessary that the old tissue be degraded. An important mechanism in this degradation is the proteolysis cascade initiated by the plasminogen activation system. uPAR binds urokinase, thereby restricting plasminogen activation to the immediate vicinity of the cell membrane. The components of the plasminogen activation system have been found to be highly expressed in many malignant tumors, indicating that tumors are able to subvert the system and use it to drive metastasis.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) analyzed both individual tumor cells (the type that escape from the tumor into the circulation system) and cancerous tissues.

They reported in the November 1, 2006, online edition of the Proceedings of the [U.S.] National Academy of Sciences that analysis of individual tumor cells indicated that uPAR amplification occurred in a significant portion of primary breast cancers. There was complete concordance between touch preps and conventional pathologic examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and circulating tumor cells provided that acquisition of HER-2 gene amplification in the circulating tumor cells was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same tumor cells and patients, suggesting a biologic bias and potential advantage for co-amplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100% and 92% of patients, respectively.

"This gene, uPAR, is an important oncogene, and that is why we determined whether or not it is amplified,” explained senior author Dr. Jonathon Uhr, professor of cancer immunobiology at the University of Texas Southwestern Medical Center.

"Unexpectedly, it is usually amplified in the same tumor cell with HER-2 gene amplification. This has significant implications for treatment with targeting agents. Moreover, we stress the value of individual tumor cell analysis for providing information that cannot be obtained by conventional pathological examination.”



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University of Texas Southwestern Medical Center