PTEN

partially activate Akt and also activate PDK1/2, which complete the Akt activation. Akt signaling effects many pathways , most notably: inhibiting BAD and other mediators of apoptosis, inhibiting GSK3β inhibition of β-catenin activity, activating MDM2 to suppress p53, and inhibiting TSC1/2 inhibition of mTOR (Figure 1). The exact effect of the Proteus Akt point mutation on these pathways is not well-characterized, and is likely tissue specific. Overactivation of these or related signaling pathways results in cellular overgrowth and tumor susceptibility as seen in Proteus syndrome as well as in related hamartomatous and hyperplastic diseases such as Beckwith-Wiedemann (IGF-2), CLOVES syndrome (PI3KCA), Cowden disease and SOLAMEN syndrome (PTEN), neurofibromatosis type I (NF1), tuberous sclerosis (TSC1/2), and Peutz-Jeghers syndrome (LKB1) (Figure 2). Note: prior to 2011, and occasionally still, the term Proteus syndrome may be used to refer to phenotypically similar PI3K-AKT-mTOR mutation syndromes, though these are now better referred to as Proteus-like, or separate disorders (e.g. SOLAMEN, CLOVES).1 Epidemiology: Proteus syndrome is exceedingly rare. Few more than 200 cases have ever been described in literature, with an estimated incidence of less than 1 per 1,000,000 live births, though the disease may be underdiagnosed if not severe (i.e. the somatic mutation occurs later in development ), or mistaken for other hamartoma syndromes.3,4 Diagnostic tests: A preliminary…

Phosphatase and Tensin Homolog is also known as PTEN, it is a phosphates encoding gene. PTEN gene is located on the long arm of chromosome 10 at the position 23.3. PTEN was first discovered in 1997, and it is a tumour suppressor gene (Li & Sun 1997, Li et al. 1997, Steck et al. 1997) it helps to regulate cell division. They function as a lipid phosphates to regulate signal transduction pathways, such as the phosphoinositide 3-kinase (PI3k), protein kinase B (AKT) . The activity of its lipid…

PTEN regulation of PI3K/AKT Pathway In the first lecture of class we discussed a diagram from Saltiel and Kahn 2001. The diagram presented the phosphoinositide 3-kinase (PI3K) and Serine/Threonine Kinase (AKT)/ Protein Kinase B (PKB) pathway inhibition of the insulin receptor and insulin receptor substrate (IRS) through activation of mammalian target of rapamycin (mTOR) and a recent study reports similar findings (Mathew et al. 2016; Saltiel and Kahn 2001). Activation of PI3K/AKT signaling…

Critical mutations usually occur within two hotspot areas of exon 9, the helical domain and exon 20, the kinase domain. These mutations occur in both smoker and non- smoker. . Somatic mutation in PIK3CA constuite 1-3% NSCLC [49]. One interesting thing that many studies reveal that PIK3CA mutations occur with EGFR mutations.[50] PTEN: is a lipid/ protein phosphatase also known as phosphatase and tension homolog deleted on chromosome number 10 that plays a role in multiple processes like growth,…

regulators of the Wnt-B catenin signaling such as WIF1, PTEN, and WNT5A. The inhibition of B-catenin signaling by the DKK1 or the SFRP1 protein overexpression reduces the expression of breast epithelial markers. An accumulation of B-catenin in the primary tumors further emphasizes the essential role of B-catenin in the process of metastasis. The canonical Wnt/B catenin signaling pathway is initiated when the Wnt ligands bind to its receptors named Frizzled and LDL receptor related protein 5 or 6…

The study explains a mutation in MC1R-RHC encourages a cancer-causing pathway when red-haired people are exposed to UV radiation. The MC1R, which helps with tanning od the skin, usually is primary in protecting melanocytes from damaged DNA. The researcher worked on a series of experiments that provided that in normal circumstances, MC1R would bind to the tumor suppressor gene PTEN. PTEN acts against cancer and without it, the cancer-causing pathway opens. They found many redheaded individuals…

pathway is also a major pathway that is involved in cell growth and proliferation, it becomes overactive or dysregulated in malignant melanoma. The PI3K is usually activated by a tyrosine kinase, RAS proteins, and cell to cell contact. After activation the PI3K it leads to the binding of a protein in the plasma membrane called AKT. This AKT protein will go onto activate mTOR by phosphorylating the protein directly. The final step leads to the cell being told to grow and proliferated. Two…

have used these analyses to spur important genomic studies into the cancer’s early development and progression. The ‘gas and brake’ drive Normal cell division is primarily controlled by a ‘gas and brake’ mechanism. Some molecular processes work as the ‘gas’ that accelerates cell division as needed. Other processes act as a ‘brake’ to prevent excessive cell division and growth, which can inevitably lead to cancerous cells if left unchecked. These antagonistic processes work to balance each…

63,046,486. Ishikawa Nagase and other scientists, in 1998, cloned a partial EHBP1 cDNA, which they called KIAA0903. They did this by sequencing clones received from a size-fractionated human brain complementary DNA (cDNA) library. They found intermediate expression in most tissues and specific brain regions. The expression was low in the tissues of the lung, spleen, and pancreas. In 2004, Soriano Guilherme and other scientists identified human EHBP1 by searching databases for sequences similar…

studied extensively for clonal evolution or independent origin of each tumor foci. Therefore, we hypothesize that different tumor foci may harbor distinct molecular aberrations making the disease much more complex and difficult to manage by current approaches. Two recent studies have reported spatial tumor molecular heterogeneity by in-depth genomic characterization using next generation sequencing approach. However, these studies did not identify driver molecular aberrations in different tumor…