Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23

We found that PPM1D, encoding a serine/threonine protein phosphatase, lies within an epicenter of the region at 17q23 that is amplified in breast cancer. We show that overexpression of this gene confers two oncogenic phenotypes on cells in culture: attenuation of apoptosis induced by serum starvation and transformation of primary cells in cooperation with RAS.

[1]  P. Meltzer,et al.  AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. , 1997, Science.

[2]  Jun O. Liu,et al.  p53-independent apoptosis induced by paclitaxel through an indirect mechanism. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J W Gray,et al.  The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells. , 2001, Cancer research.

[4]  Y. Chen,et al.  Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis. , 2000, Journal of the National Cancer Institute.

[5]  Masaaki Adachi,et al.  p53‐inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK‐p53 signaling in response to UV radiation , 2000, The EMBO journal.

[6]  S. Månér,et al.  Frequent co-amplification of two different regions on 17q in aneuploid breast carcinomas. , 2001, Cancer genetics and cytogenetics.

[7]  T. Hunter,et al.  Oncogenic kinase signalling , 2001, Nature.

[8]  Albert J. Fornace,et al.  Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity , 2002, Nature Genetics.

[9]  F. Couch,et al.  Structural analysis of the 17q22-23 amplicon identifies several independent targets of amplification in breast cancer cell lines and tumors. , 2001, Cancer research.

[10]  M. Schwab.  Oncogene amplification in solid tumors. , 1999, Seminars in cancer biology.

[11]  S. Pimplikar,et al.  PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Michael L. Bittner,et al.  Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J W Gray,et al.  Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Marc J. van de Vijver,et al.  Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancers , 2000, Nature Genetics.

[15]  Ash A. Alizadeh,et al.  Genome-wide analysis of DNA copy-number changes using cDNA microarrays , 1999, Nature Genetics.