NDLI: Loss of Inhibitory IRS-1 Phosphorylation is an Early Event in mTOR-Dependent Endometrial Hyperplasia and Carcinoma

Please wait, while we are loading the content...

Year: 2017 Volume: 10

Year: 2016 Volume: 9

Year: 2010 Volume: 3 Issue: 12

Year: 2010 Volume: 3 Issue: 11

Year: 2010 Volume: 3 Issue: 10

Year: 2010 Volume: 3 Issue: 9

Year: 2010 Volume: 3 Issue: 8

Year: 2010 Volume: 3 Issue: 7

Year: 2010 Volume: 3 Issue: 6

Year: 2010 Volume: 3 Issue: 5

Year: 2010 Volume: 3 Issue: 4

Year: 2010 Volume: 3 Issue: 3

Elevated phosphate activates N-ras and promotes cell transformation and skin tumorigenesis.

Differential Inhibition of Protein Translation Machinery by Curcumin in Normal, Immortalized and Malignant Oral Epithelial Cells

Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.

Parity-induced decrease in systemic growth hormone alters mammary gland signaling: a potential role in pregnancy protection from breast cancer.

Gene expression patterns in the human breast after pregnancy.

American ginseng suppresses colitis through p53-mediated apoptosis of inflammatory cells.

Obesity, endogenous hormone metabolism, and prostate cancer risk: a conundrum of 'highs' and 'lows'.

Finasteride modifies the relation between serum C-peptide and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

Loss of Inhibitory IRS-1 Phosphorylation is an Early Event in mTOR-Dependent Endometrial Hyperplasia and Carcinoma

Chronic cyclooxygenase-2 inhibition promotes myofibroblast-associated intestinal fibrosis.

Effects of cigarette smoke on the human oral mucosal transcriptome.

Adaptor proteins as targets for cancer prevention.

The impact of fish oil on the chemopreventive efficacy of tamoxifen against development of N-methyl-N-nitrosourea-induced rat mammary carcinogenesis.

Selenomethionine and alpha-tocopherol do not inhibit prostate carcinogenesis in the testosterone plus estradiol-treated NBL rat model.

Upper airway gene expression in smokers: the mouth as a 'window to the soul' of lung carcinogenesis?

Year: 2010 Volume: 3 Issue: 2

Year: 2010 Volume: 3 Issue: 1

Year: 2009 Volume: 2

Year: 2008 Volume: 1

Loss of Inhibitory IRS-1 Phosphorylation is an Early Event in mTOR-Dependent Endometrial Hyperplasia and Carcinoma

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	McCampbell, Adrienne S. Harris, Heather A. Crabtree, Judy S. Winneker, Richard C. Walker, Cheryl L. Broaddus, Russell R.
Description	Country affiliation: United States Author Affiliation: McCampbell AS ( Department of Pathology, Science Park Research Division, The University of Texas M.D. Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX 78957, USA.)
Abstract	IGF-I receptor signaling contributes to the development of endometrial hyperplasia, the precursor to endometrioid-type endometrial carcinoma, in humans and in rodent models. This pathway is under both positive and negative regulation, including S6K phosphorylation of IRS-1 at serine (636/639), which occurs downstream of mTOR activation to inhibit this adapter protein. We observed activation of mTOR with a high frequency in human endometrial hyperplasia and carcinoma, but an absence of IRS-1 phosphorylation, despite high levels of activated S6K. To explore when during disease progression mTOR activation and loss of negative feedback to IRS-1 occurred, we utilized the Eker rat $(Tsc2^{Ek/+})$ model, where endometrial hyperplasia develops as a result of loss of Tsc2, a “gatekeeper” for mTOR. We observed mTOR activation early in progression in hyperplasias and in some histologically normal epithelial cells, suggesting that event(s) in addition to loss of Tsc2 were required for progression to hyperplasia. In contrast, while IRS-1 S636/639 phosphorylation was observed in normal epithelium, it was absent from all hyperplasias, indicating loss of IRS-1 inhibition by S6K occurred during progression to hyperplasia. Treatment with an mTOR inhibitor (WAY-129327) significantly decreased hyperplasia incidence and proliferative indices. Since progression from normal epithelium to carcinoma proceeds via endometrial hyperplasia, these data suggest a progression sequence where activation of mTOR is followed by loss of negative feedback to IRS-1 during the initial stages of development of this disease.
File Format	HTM / HTML
ISSN	19406207
e-ISSN	19406215
DOI	10.1158/1940-6207.CAPR-09-0199
Journal	Cancer Prevention Research
Issue Number	3
Volume Number	3
Language	English
Publisher	American Association for Cancer Research
Publisher Date	2010-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Oncology Endometrial Hyperplasia Metabolism Endometrial Neoplasms Endometrium Insulin Receptor Substrate Proteins Intracellular Signaling Peptides And Proteins Protein-serine-threonine Kinases Animals Blotting, Western Pathology Immunoenzyme Techniques Phosphorylation Rats, Mutant Strains Signal Transduction Tor Serine-threonine Kinases Tumor Suppressor Proteins Physiology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment.

Insulin and metabolic stress stimulate multisite serine/threonine phosphorylation of insulin receptor substrate 1 and inhibit tyrosine phosphorylation.

Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR.

mTOR signaling in autophagy regulation in the kidney.

Altered mTOR signaling in senescent retinal pigment epithelium.

Activation of the cardiac mTOR/p70(S6K) pathway by leucine requires PDK1 and correlates with PRAS40 phosphorylation.

Insulin-induced serine phosphorylation of IRS-2 via ERK1/2 and mTOR: studies on the function of Ser675 and Ser907.

A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle

Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine

Loss of Inhibitory IRS-1 Phosphorylation is an Early Event in mTOR-Dependent Endometrial Hyperplasia and Carcinoma

Similar Documents

p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment.

Insulin and metabolic stress stimulate multisite serine/threonine phosphorylation of insulin receptor substrate 1 and inhibit tyrosine phosphorylation.

Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR.

mTOR signaling in autophagy regulation in the kidney.

Altered mTOR signaling in senescent retinal pigment epithelium.

Activation of the cardiac mTOR/p70(S6K) pathway by leucine requires PDK1 and correlates with PRAS40 phosphorylation.

Insulin-induced serine phosphorylation of IRS-2 via ERK1/2 and mTOR: studies on the function of Ser675 and Ser907.

A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle

Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine

Loss of Inhibitory IRS-1 Phosphorylation is an Early Event in mTOR-Dependent Endometrial Hyperplasia and Carcinoma