Chromosome Condensation 1-Like (Chc1L) Is a Novel Tumor Suppressor Involved in Development of Histiocyte-Rich Neoplasms
| Autor: | Youdong Wang, Xiao-Yan Wen, Ding Yan Wang, Hiroki Shimizu, Anthony O. Gramolini, Susan Newbigging, Hae-Ra Cho, David Spillane, Mingyao Liu, Chang-Xin Shi |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Chronic lymphocytic leukemia lcsh:Medicine Loss of Heterozygosity Cell Cycle Proteins Biology Histiocytic sarcoma medicine.disease_cause Loss of heterozygosity Prostate cancer Mice Bone Marrow medicine Animals Guanine Nucleotide Exchange Factors lcsh:Science Mice Knockout Multidisciplinary Tumor Suppressor Proteins lcsh:R Nuclear Proteins Heterozygote advantage Histiocytes medicine.disease Lymphoma Neoplasm Proteins Mice Inbred C57BL Chromosomal region lcsh:Q Lymphoma Large B-Cell Diffuse Chromosome Deletion Carcinogenesis Spleen Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 8, p e0135755 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Human chromosomal region 13q14 is a deletion hotspot in prostate cancer, multiple myeloma, and chronic lymphocytic leukemia. This region is believed to host multiple tumor suppressors. Chromosome Condensation 1-like (CHC1L) is located at 13q14, and found within the smallest common region of loss of heterozygosity in prostate cancer. Decreased expression of CHC1L is linked to pathogenesis and progression of both prostate cancer and multiple myeloma. However, there is no direct evidence for CHC1L’s putative tumor suppressing role in current literature. Presently, we describe the generation and characterization of Chc1L knockout mice. Chc1L -/- mice do not develop cancer at a young age, but bone marrow and spleen cells from 8–12 week-old mice display an exaggerated proliferative response. By approximately two years of age, knockout and heterozygote mice have a markedly increased incidence of tumorigenesis compared to wild-type controls, with tumors occurring mainly in the spleen, mesenteric lymph nodes, liver and intestinal tract. Histopathological analysis found that most heterozygote and knockout mice succumb to either Histiocytic Sarcoma or Histiocyte-Associated Lymphoma. Our study suggests that Chc1L is involved in suppression of these two histiocyte-rich neoplasms in mice and supports clinical data suggesting that CHC1L loss of function is an important step in the pathogenesis of cancers containing 13q14 deletion. |
| Databáze: | OpenAIRE |
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