Stains & molecular markers
ING1


Topic Completed: 1 March 2016

Minor changes: 2 September 2020

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PubMed Search: ING1[title]

Related topics: ING2, ING3


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Cite this page: Enwere E, Thakur S. ING1. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsing1.html. Accessed October 28th, 2020.
Definition / general
  • INhibitor of Growth (ING) proteins are tumor suppressors which regulate various cellular processes including cellular proliferation, apoptosis and senescence
  • They are characterized as Type II tumor suppressor genes, in that their expression is suppressed in tumors without mutation or deletion of their DNA coding regions
  • Mechanisms leading to their loss of expression in tumors include loss of heterozygosity, epigenetic silencing, inhibition of mRNA transcription and protein mislocalization (Cancer Lett 2014;345:1)
  • There are 5 different members of the ING family (ING1-ING5) and all of them have different isoforms. In particular, ING1 has four isoforms (ING1a-d) out of which ING1a and ING1b are the best studied
  • ING1a, when overexpressed in cells, impairs cell growth by inducing senescence, whereas ING1b isoform induces cell death via apoptosis
  • All ING proteins have a conserved Plant HomeoDomain (PHD) motif which interacts with the lysine residues of histones
    • For this reason, the INGs are active members of various histone acetylase and histone deacetylase (chromatin remodeling) complexes
  • All ING proteins contain a Lamin Interacting Domain (LID), which allows their interaction with LaminA/C protein in the nucleus (FEBS Lett 2014;588:2728)
  • ING1b protein is known to interact with and stabilize TP53 protein, which is a classical cell cycle regulator and inducer of apoptosis (PLoS One 2011;6:e21065)
Clinical features
  • ING1 is down - regulated in a variety of cancers such as glioblastoma, breast, ovarian, gastric, lung and head and neck cancers
  • The ING1 gene is transcriptionally repressed in Hutchinson Gilford Progeria Syndrome (HGPS) and other laminopathies (FEBS Lett 2014;588:2728, Cancer Lett 2014;345:1)
Uses by pathologists
  • Low levels of ING1 protein expression are associated with poor prognosis in neuroblastoma and breast cancer (Oncol Rep 2004;12:811)
  • In estrogen receptor - positive breast cancers, stromal ING1 expression is associated with poor post - treatment prognosis, whereas in estrogen receptor - negative breast cancers, tumor ING1 is associated with better prognosis (Mol Cancer 2015;14:164, Oncotarget 2014;5:4244)
  • In oral squamous cell carcinoma, mislocalization of ING1 to the tumor cytoplasm is associated with better patient survival (Oncotarget 2014;5:3210)
  • In childhood acute lymphoblastic leukemia, loss of nuclear ING1 expression is associated with better prognosis (J Clin Pathol 2002;55:596)
Pathophysiology
  • ING1 knockout (KO) mice show features like reduced body size, hypersensitivity to radiation exposure and increased incidence of B - cell lymphoma
  • No other morphological, physiological or behavioral abnormalities were reported in ING1 KO mice (Oncogene 2006;25:857)
Microscopic (histologic) description
  • The ING family (ING1 - 5) of tumor suppressors are involved in a broad range of cellular processes
  • The tumor - suppressive properties of INGs are due to their ability to induce apoptosis, senescence and inhibition of cell migration
  • Due to their ability to interact with histones, all ING proteins are categorized as "histone readers" and can regulate gene expression epigenetically
Microscopic (histologic) images

Contributed by Dr. Karl Riabowol

ING1 antibody (CAb5)

Positive staining - normal
  • B - cells, NK cells, Monocytes, Testis, Ovary, Lymph node, Brain, Placenta, Lung Rectum, Retina, Heart, Bone Marrow, Spleen, Tonsil
Positive staining - disease
  • T - cell leukemia (Jurkat Cells), Cervical Cancer (HeLa), Prostate Cancer (LnCap), Breast Cancer (MCF7), Colon Cancer (RKO), Liver Cancer (HepG2), Bone Cancer (U2OS)
Negative staining
  • Most tissues show moderate to weak nuclear ING1 - 2 staining
  • Skeletal muscle, adipose tissue, Lymph Nodes, Thymus stain negative for ING3
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