STAT1-deficient mice spontaneously develop estrogen receptor a-positive luminal mammary carcinomas

Paper of the Month: March, 2012

Breast Cancer Res. 2012 Jan 20;14(1):R16. [Epub ahead of print]

Chan SRVermi WLuo JLucini LRickert CFowler AMLonardi SArthur CYoung LJLevy DEWelch MJCardiff RDSchreiber RD.

 

 

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Comments by Dr. Murray Gardner:

This paper is an excellent example of the power of GEM to model human disease and dissect the role of individual genes in pathogenesis.   As reported here, STAT1 null mice develop an increased incidence (65%) of spontaneous breast tumors with a median tumor onset of 23 months. Remarkably , the tumors are indistinguishable histopathologically from infiltrating ductular carcinomas, the most common type of human breast cancer. Moreover, the GEM luminal cancer cells are ER+ and PR+ as seen in 60 –70% of human breast cancers.. This is the 1st GEM model of human breast cancer to have these  analogous features and thus it fills a need for further research. Interestingly, the authors find that about 50 % of human ER+ breast tumors lack STAT1 expression in the neoplastic cells whereas STAT1 expression is elevated in the adjacent normal breast epithelial cells. Together, these findings reveal , rather unexpectedly, that STAT1 may have a tumor suppressive rather than an oncogenic function.This idea is supported by the induction of apoptosis in  STAT1 mammary tumor cells by transfection with wildtype, but not mutant STAT1 .Most tellingly, the authors show in this GEM model that elevated levels of STAT1 are  often detected in the  infiltrating stromal  (not myoepithelial ) cells suggesting that elevated STAT1 expression in the analogous human breast tumors may have a similar explanation.Obviously, accurate assessment of human breast tumors will require single cell analysis of STAT1 expression.  In my opinion, there could be no better example of the value of GEM  to model human breast cancer then shown here. I still think it’s magic!

 

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