New stem cell research has been reported by scientists at Harvard University
2009 JUL 27 - (NewsRx.com) -- According to a study from the United States, "Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli) in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively." "Only the K14-cre-mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of beta-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; Apc(CKO/+) mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre-induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre-mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands," wrote M. Kuraguchi and colleagues, Harvard University. The researchers concluded: "Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of beta-catenin signaling optimal for mammary tumor development and explain partially the colon-but not mammary-specific tumor development in patients that carry germline mutations in APC." Kuraguchi and colleagues published the results of their research in Plos Genetics (Genetic Mechanisms in Apc-Mediated Mammary Tumorigenesis. Plos Genetics, 2009;5(2):367). For additional information, contact M. Kuraguchi, Harvard University, School Medical, Harvard Partners Center Genetics & Genom, Boston, MA 02115, USA. The publisher of the journal Plos Genetics can be contacted at: Public Library Science, 185 Berry St., Ste. 1300, San Francisco, CA 94107, USA. Keywords: United States, Boston, Adenocarcinoma, Adenomatous Polyposis Coli, Breast Cancer, Breast Carcinoma, Endocrinology, Genetics, Oncology, Progenitor Cell, Stem Cell Research, Tumor Suppression, Women's Health, Harvard University. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2009, Clinical Oncology Week via NewsRx.com.
|
