- Paper Report
- Open Access
What do Dictyosteliumand mammary gland have in common?
- Karen L Schmeichel1
© Biomed Central Ltd 2001
- Received: 9 May 2001
- Accepted: 20 August 2001
- Published: 1 December 2001
- Collagen, extracellular matrix, gene targeting, lactation, mammary gland development, receptor tyrosine kinases
The discoidin domain receptors, DDR1 and DDR2, display characteristics pertinent to the study of both extracellular matrix (ECM) and tyrosine-kinase-dependent intracellular signalling. DDR extracellular domains share homology with the Dictyostelium discoideumprotein discoidin, a lectin-like factor that is secreted by cells to form a primitive ECM during aggregation. In higher organisms, DDR1 and DDR2 function as receptors for collagen-rich substrates; ligation of collagens activates the tyrosine kinase domains intrinsic to the proteins. Thus DDRs mediate signalling events that are stimulated in response to cues from the ECM and are likely to be important determinants of cellular differentiation. This paper explores this hypothesis by examining the phenotypes of the DDR1-/- mouse.
Consistent with the detection of DDR1 binding sites in the uterine wall and in mammary glands during pregnancy, DDR1-/- females exhibit defects in uterine blastocyst implantation and mammary gland function. DDR1-/- females are lactationally impaired; although milk gene transcripts are expressed in the mammary epithelium, encoded proteins are not effectively produced and secreted into alveolar lumena. The authors attribute this defect to improper mammary gland development, citing delayed ductal outgrowth and ductal hyperproliferation as potential causes. Mammary epithelium from DDR1-/-mice shows increased collagen deposition. The authors conclude that, under normal circumstances, DDR1 negatively regulates two functions required for mammary gland function: epithelial proliferation and the synthesis of collagenous matrix components. On the basis of these observations, the authors suggest a role for DDR1 in human breast carcinoma progression.
Alkaline phosphatase staining, histological and immunological staining, whole mount mammary gland analysis, western blotting, northern blotting, gene targeting