Cripto-1 Enhances Migration and Branching Morphogenesis of Mouse Mammary Epithelial Cells

Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma

“…Since CR-1 or Cr-1 overexpression in several different mouse mammary epithelial cell lines leads to enhanced branching in type I collagen gels in vitro (Wechselberger et al, 2001), we assessed whether mammary epithelialspecific overexpresssion of CR-1 could perturb ductal morphogenesis in virgin Tg mice by performing whole mount and histological analyses on MMTV/CR-1 animals. TEB morphology was indistinguishable between Tg and wild-type animals at 4 weeks of age at this stage (Figure 2a and b).…”

“…Whether these specific oncogenes are involved in the regulation of CR-1 expression is not known. In vitro, CR-1 overexpression can induce anchorage-independent growth of nontransformed mouse mammary epithelial cells (Ciardiello et al, 1991;Niemeyer et al, 1998;Wechselberger et al, 2001). In addition, stable overexpression of Cr-1 or CR-1 in several nontransformed mouse mammary epithelial cell lines stimulates chemotaxis, chemokinesis and branching morphogenesis, suggesting a possible role for these proteins during the process of epithelial-mesenchymal transition (EMT) Wechselberger et al, 2001;Strizzi et al, 2004).…”

“…In vitro, CR-1 overexpression can induce anchorage-independent growth of nontransformed mouse mammary epithelial cells (Ciardiello et al, 1991;Niemeyer et al, 1998;Wechselberger et al, 2001). In addition, stable overexpression of Cr-1 or CR-1 in several nontransformed mouse mammary epithelial cell lines stimulates chemotaxis, chemokinesis and branching morphogenesis, suggesting a possible role for these proteins during the process of epithelial-mesenchymal transition (EMT) Wechselberger et al, 2001;Strizzi et al, 2004). Finally, primary mouse mammary epithelial cells which retrovirally overexpress Cr-1 when introduced into the cleared mammary fat pad of syngeneic, ovariectomized virgin mice give rise to outgrowths that exhibit an increase in secondary and tertiary lateral side branching .…”

Notch4 intracellular domain binding to Smad3 and inhibition of the TGF-β signaling

“…Stable transfectants of pEF-1 control vector, pEF-ICD4, pEF1-dRAM-ICD4 in HC-11 mouse mammary epithelial cells (a gift from Dr Nancy Hynes, Friedrich Miescher Institute, Basel, Switzerland) and EpH4 mouse mammary epithelial cells were cultured and stably transfected as described (Imatani and Callahan, 2000;Wechselberger et al, 2001). Colonies were selected and tested by RT-PCR and Western blot analysis (Bianco et al, 2002) for transgene expression.…”

Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology

“…Cripto expression was first found in human and mouse EC cells and male teratocarcinomas and was demonstrated to be over-expressed in breast, cervical, ovarian, gastric, lung, colon and pancreatic carcinomas, in contrast to normal tissues where cripto expression was invariably absent (for a review see Salomon et al, 1999). Cripto can apparently function as an oncogene by inducing cell transformation, migration, invasion and epithelial-tomesenchimal transition (EMT) in mammary epithelial cells and in breast and cervical carcinomas cells (Ebert et al, 2000;Wechselberger et al, 2001;Strizzi et al, 2004). EMT is one of the key processes in morphogenesis and tumor progression; it involves a dramatic change in cells phenotype by which a well-differentiated and polarized epithelial cell is converted into a mesenchymal cell with a leading edge that facilitates its migration through the extracellular matrix, and thus the colonization of different structures.…”