Abstract:
The present analyses were done to define the role of
fetuin-A (Fet) in mammary tumorigenesis using the
polyoma middle T antigen (PyMT) transgenic mouse
model. We crossed Fet-null mice in the C57BL/6 background
with PyMT mice in the same background
and after a controlled breeding protocol obtained
PyMT/Fet / , PyMT/Fet / , and PyMT/Fet / mice
that were placed in control and experimental groups.
Whereas the control group (PyMT/Fet / ) formed
mammary tumors 90 days after birth, tumor latency
was prolonged in the PyMT/Fet and PyMT/Fet
mice. The majority of the PyMT/Fet mice were
tumor-free at the end of the study, at approximately
40 weeks. The pathology of the mammary tumors in
the Fet-null mice showed extensive fibrosis, necrosis,
and squamous metaplasia. The preneoplastic mammary
tissues of the PyMT/Fet / mice showed intense
phopho-Smad2/3 staining relative to control tissues,
indicating that transforming growth factor- signaling
is enhanced in these tissues in the absence of Fet.
Likewise, p19ARF and p53 were highly expressed in
tumor tissues of PyMT/Fet mice relative to the
controls in the absence of Fet. The phosphatidylinositol
3-kinase/Akt signaling pathway that we previously
showed to be activated by Fet, on the other
hand, was unaffected by the absence of Fet.
