Hereditary Colorectal Cancer
Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams in Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
PTEN is a gene encoding for phosphatase and tensin homolog, a protein with a key role in control of the cell cycle. PTEN functions as a tumour suppressor gene by negative regulation of the Akt/PKB signaling pathway.108 Its importance in the control of cell growth is evident by the number of cancers with which PTEN mutations are associated. In the colorectum, germline PTEN mutations cause syndromes of colorectal hamartomatous polyposis, multiple skin tumours, skeletal anomalies and cancers in multiple organs. These syndromes can be grouped under the heading PTEN Hamartoma Tumour Syndrome, although they need to be discussed separately. They are Cowden’s Syndrome (CS), Bannayan–Riley–Ruvalcaba Syndrome (BRRS), Gorlin Syndrome and Proteus Syndrome. CS and BRRS are the most common and present overlapping phenotypes. When patients present with multiple colorectal polyps that include hamartomas, fibromas, neuromas, ganglioneuromas and lipomas, genetic testing for a PTEN mutation is indicated. PTEN is now part of all colorectal cancer panels and so panel testing should reveal the deleterious mutation. This is important because many cases have no family history.
Current Active Surveillance Protocol for Prostate Cancer
Ayman El-Baz, Gyan Pareek, Jasjit S. Suri in Prostate Cancer Imaging, 2018
As with PCA3, the transcription products of T2ERG can be collected in the urine after prostate massage. T2ERG is a fusion protein of the TMPRSS2 gene (21q22.3) and the ERG gene (21q22.2) that is present in ~40% to 80% of prostate cancers (Yu et al. 2010). TMPRSS2 is an androgen-sensitive gene and ERG is an ETS family transcription factor that is considered a key prostate cancer oncogene (Squire 2009). Like the BCR:ABL gene translocation in chronic myeloid leukemia (CML), a deletion in the long arm of chromosome 21 places the ERG gene immediately downstream of the androgen responsive TMPRSS2 gene. ERG will then drive the overexpression of TMPRSS2. This overexpression with loss of PTEN leads to unregulated cellular proliferation, anti-apoptotic activity, and additional cell cycle events that lead to malignant cells (Squire 2009). A study of 265 patients on AS with median follow-up of 4.1 years found ERG-positive tumors had a 58.6% risk of disease progression versus 21.7% in the ERG-negative cohort (hazard ratio 2.45) (Berg 2016). There is limited literature on the long-term outcomes of urinary T2ERG’s predictive value in AS and further research is warranted.
Genetics of Endocrine Tumours
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Cowden’s disease (CD), also known as multiple hamartoma syndrome, is a rare autosomal dominantly inherited disease. Multiple trichilemmomas of the skin are common diagnostic features found in >90% of affected individuals. Patients with CD have an increased risk for carcinomas of the breast and thyroid; up to a 10% lifetime risk of follicular or papillary thyroid cancer. Approximately 70% of people with Cowden syndrome will have benign thyroid abnormalities, including multinodular goitre, adenomatous nodules and follicular adenomas. Marsh et al. identified PTEN mutations in 30 of 37 (81%) Cowden disease families.89 The PTEN gene is involved in the previously PI3/AKT or PI3-AKT intracellular signalling pathway. Although no consensus clinical guideline exists testing for germline PTEN mutations are available commercially.
Identification of long noncoding RNA NEAT1 as a key gene involved in the extramedullary disease of multiple myeloma by bioinformatics analysis
Published in Hematology, 2023
Ting Chen, Zhengxu Sun, Yunqi Cui, Jiamei Ji, Yating Li, Xiaoyan Qu
The dysregulation of PTEN/PI3K/Akt signaling pathway is closely related to the occurrence and development of tumors [10]. PTEN is a tumor suppressor gene discovered recently. Another study showed that the knockdown of NEAT1 suppresses laryngocarcinoma cell growth and metastasis via miR-524-5p/HDAC1/PTEN/AKT signaling pathway [23]. In addition, NEAT1 has been identified as an upstream modulator or downstream effector of major signaling pathways, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin, and p53, influencing endometrial cancer metastasis [24]. Loss of PTEN function leads to the overactivation of PI3K/Akt pathway and promotes the development of various tumors [25]. Recent studies demonstrated that many molecular signaling pathways regulate gene expression at the transcriptional, posttranscriptional, and epigenetic levels and are involved in tumor initiation, metastasis, and drug resistance [26–28]. Nonetheless, there is no evidence associating PTEN with the extramedullary migration of MM. Herein, we found that after downregulation of lncRNA-NEAT1 in RPMI8226 and U266 cells, the expression of PTEN protein was significantly upregulated, and the expression of p-PI3K and p-Akt protein was significantly downregulated, suggesting that NEAT1 regulates the Akt signaling pathway through PTEN.
Determination of cytokine profile and associated genes of the signaling pathway in HNSCC
Published in Journal of Receptors and Signal Transduction, 2022
Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven
PDGFRB, a homodimer of PDGFB, is associated with a poor prognosis of many common malignancies especially fibroblast-rich stroma [20], and it is also a crucial factor for tumor growth, angiogenesis and tumor survival. PDGFRB has been found to interact with members of several different RTK families, including EGFR [21]. PTEN is an important tumor suppressor gene, which functions in many cellular processes such as cell proliferation, survival, growth, metabolism, cell migration by inactivating PI3-kinase-dependent signaling. In the literature, associations between PTEN and PDGF isoforms were reported in human prostate cancer cell lines [22]. Lin et al. reported that the expressions of PDGFA and PDGFB mRNAs were higher in oral squamose cell carcinoma tissue than in the adjacent normal tissues [23]. Taken together, our results suggest a mechanism by which loss of PTEN may promote HNSCC progression via PDGFR signal transduction in HNSCC.
Mief1 augments thyroid cell dysfunction and apoptosis through inhibiting AMPK-PTEN signaling pathway
Published in Journal of Receptors and Signal Transduction, 2020
Yonglan Zhang, Haichao Zhang, Wenjie Shi, Wei Wang
AMPK pathway has been linked to energy metabolism. A decrease in the levels of ATP and an increase in the levels of ADP could promote the activation of AMPK [9]. Of note, AMPK activity is very important for thyroid function because it sustains protein synthesis and release [10]. Decreased AMPK pathway is associated with cell death through various mechanisms. In the present study [11], we asked whether Mief1 modulates the viability of thyroid cells through the AMPK pathway [12,13]. In addition to AMPK pathway, PTEN is also necessary for thyroid cell function. PTEN regulates cell proliferation and reduces apoptosis under stressful conditions. Besides, PTEN also triggers autophagy which is a protective process to degrade abnormal protein molecular. However, little study is available to explore the influence of PTEN in thyroid cell function and viability. Therefore, our study is conducted to understand the influence of Mief1 in thyroid cell death and dysfunction and verify whether AMPK and PTEN are controlled by Mief1 and promotes thyroid cell survival [14].
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