1. Cripto: roles in mammary cell growth, survival, differentiation and transformation
- Author
-
Christina C. Niemeyer, M. Graziella Persico, and Eileen D. Adamson
- Subjects
Cell Survival ,Cell ,Apoptosis ,Biology ,Cripto ,medicine.disease_cause ,Transfection ,Viral vector ,Cell Line ,Mice ,Mammary Glands, Animal ,Pregnancy ,medicine ,In Situ Nick-End Labeling ,Animals ,Growth Substances ,Molecular Biology ,Membrane Glycoproteins ,Epidermal Growth Factor ,Cell growth ,Cell Differentiation ,Epithelial Cells ,Cell Biology ,Oligonucleotides, Antisense ,Cell biology ,Neoplasm Proteins ,Transplantation ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Gene Expression Regulation ,Female ,Carcinogenesis ,Growth Factor Gene ,Cell Division - Abstract
Cripto-1 (Cr-1) protein, encoded by the teratocarcinoma-derived growth factor gene (TDGF-1), is highly correlated with transformation in breast cancer. Eighty-two percent of breast carcinomas express Cr-1 whereas it is undetected in normal human breast tissue. We confirmed and extended findings that Cr-1 protein is expressed during the pregnancy and lactating stages of normal murine mammary glands but is barely detectable in glands from virgin animals and is undetectable in involuted glands. Cr-1 was found to be expressed in CID 9 cells, a line of mammary epithelial cells derived from 14.5 day pregnant mice and we have used these cells to investigate the roles of this gene. Exogenous mouse Cr-1 expression from a retroviral vector caused CID 9 cells to grow at an increased rate and to increased cell densities compared to parental and control cells. CID 9 cells overexpressing Cr-1 did not differentiate efficiently. Infection of CID 9 cells with a Cr-1 antisense vector caused these cells to change in morphology, to grow slowly, to undergo apoptosis at a higher rate and to achieve lower saturation densities but the cells were still capable of differentiating. We concluded that Cr-1 is an autocrine growth factor for normal breast cells, that when over-expressed stimulates excessive cell proliferation at the expense of differentiation. In transplantation studies, Cr-1 over-expression stimulated the growth and survival of mammary cells, but did not stimulate tumorigenesis in vivo.
- Published
- 1998