Track topics on Twitter Track topics that are important to you
Plk2 is a target of p53. Our previous studies demonstrated that with wild-type p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient tumors grew larger than control. Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. We investigated Plk2's tumor suppressor functions in relationship to mTOR signaling. Archival specimens from 12 colorectal adenocarcinomas were stained for markers including Plk2, phosphorylated mTOR (serine 2448) and ribosomal S6 (Serine 235/236). We show that Plk2 is expressed in normal colon, with a punctate staining pattern in supranuclear cytoplasm. In colorectal adenocarcinoma, Plk2 demonstrates complete or partial loss of expression. Strong expression of phosphorylated mTOR is observed in the invasive front. Phosphorylated S6 expression partially correlates with phosphorylated mTOR expression but appears more diffuse in some cases. p53 and Ki67 expression is diffuse, in the subset of cases examined. In order to determine whether Plk2 is lost prior to the development of invasive cancer, 8 colon polyps from 6 patients were evaluated for Plk2 expression. All polyps are positive for Plk2. A Cancer Genome Atlas search identified Plk2 mutations to be infrequent in colorectal adenocarcinomas. Neither Plk2 methylation (in the gene body) nor copy number variations correlated with changes in mRNA expression levels. Loss of Plk2 expression along with accentuated expression of phosphorylated mTOR and phosphorylated S6 at the invasive front in some colorectal carcinomas is consistent with previous findings that an interaction between Plk2 and TSC1 / mTOR signaling molecules plays a role in tumor suppression. Plk2 protein expression is lost at the same stage in colorectal carcinogenesis as p53. The p53 dependence of Plk2 loss and tumor suppressor function in relationship to mTOR signaling may have therapeutic implications.
This article was published in the following journal.
Name: Neoplasia (New York, N.Y.)
Colorectal adenomas are precursor lesions of colorectal cancers and represent clonal amplifications of single cells from colonic crypts. DNA methylation patterns specify cell-type identity during cell...
Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of...
Lynch syndrome (LS) is associated with a high risk of colorectal cancer (CRC). The aim of this study was to assess the cumulative risk for the development of colorectal adenomas or carcinomas in a LS ...
Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly...
Germline mutations in the DNA polymerase genes POLD1 and POLE confer high risk for multiple colorectal adenomas and colorectal cancer. However, prevalence and the clinical phenotype of mutation carrie...
Duodenal carcinomas are the leading cause of mortality in patients with Familial Adenomatous Polyposis (FAP) who underwent prophylactic colorectal surgery. The purpose of this study is to ...
The coloscopy is considered as the gold standard for screening and resection of colorectal adenomas. However the literature reports that the rate of omitted adenoma is still high (24 to 41...
The purpose of the study is to investigate if long-term treatment with three known drugs (acetylsalicylic acid, 1α 25-dihydroxy cholecalciferol, and calcium carbonate) prevents recurrence...
Previous studies have shown geographic disparities in the detection of colorectal adenomas in Côte-d'Or, with an impact of the distance from the general practitioner and an ecological dep...
The purpose of this study is to confirm that linear quantification of CD3+ cells is a prognostic biomarker in localized colorectal carcinomas.
Clusters of colonic crypts that appear different from the surrounding mucosa when visualized after staining. They are of interest as putative precursors to colorectal adenomas and potential biomarkers for colorectal carcinoma.
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.
A carcinoma composed mainly of epithelial elements with little or no stroma. Medullary carcinomas of the breast constitute 5%-7% of all mammary carcinomas; medullary carcinomas of the thyroid comprise 3%-10% of all thyroid malignancies. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1141; Segen, Dictionary of Modern Medicine, 1992)
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with the formation of colorectal cancer (MCC stands for mutated in colorectal cancer).