Stains
ING1

Author: Satbir Thakur, Ph.D. and Emeka Enwere, M.D. (see Authors page)

Revised: 13 April 2016, last major update March 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: ING1[title]

Related topics: ING2, ING3

Cite this page: ING1. PathologyOutlines.com website. http://pathologyoutlines.com/topic/stainsing1.html. Accessed June 24th, 2017.
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

Images hosted on Pathout server:

ING1 antibody (CAb5) - contributed by Dr. Karl Riabowol

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