Cc. Niemeyer et al., Preneoplastic mammary tumor markers: Cripto and Amphiregulin are overexpressed in hyperplastic stages of tumor progression in transgenic mice, INT J CANC, 81(4), 1999, pp. 588-591
Amphiregulin (Ar) and Cripto (Cr) are autocrine growth factors for mammary
cells and both have been observed to exhibit high expression in human mamma
ry tumors, in contrast with adjacent tissues. To investigate whether Ar and
Cr play roles in the progression of mammary cell proliferation to unregula
ted growth and tumor formation, the levels of expression were examined in t
ransgenic mice (TGM) that over-express several different oncogenes: MMTV-Po
lyoma virus middle T antigen (MMTV-PyMT), MMTV-c-ErbB2 (c-neu, HER2) and MT
-hTGF alpha. These transgenic mice all produce mammary tumors but with diff
erent rates of progression. The levels of Ar were induced up to 10-fold in
association with hyperplasia in 2 of the TGM. Cr overexpression was consist
ently observed in hyperplastic mammary glands in all the animal models, dec
reasing in overt tumors in 2 of the TGM models. In MMTV-PyMT mammary glands
, the levels of Cr expression rose 7- to 10-fold in hyperplastic tissue and
25-fold the levels in tumors compared to age-matched transgene negative mi
ce. Ar and especially Cr thus should have potential value as markers of pre
neoplastic change in mammary tissue. (C) 1999 Wiley-Liss, Inc.