Premium
The candidate tumor suppressor gene ING4 is down‐regulated in human lung cancer and correlates with an increase in ELR+ CXC chemokines
Author(s) -
Mestas Javier,
Burdick Marie D.,
Strieter Robert M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a215-a
Subject(s) - cxcl1 , cancer research , carcinogenesis , chemokine , cxc chemokine receptors , hif1a , biology , lung cancer , cxcl5 , adenocarcinoma , tumor progression , cyclin d1 , inflammation , cancer , pathology , medicine , immunology , cell cycle , angiogenesis , chemokine receptor
RATIONALE The relationship between inflammation and cancer has long been recognized. Recent studies have elucidated the importance of a key inflammatory transcription factor, nuclear factor‐κB (NF‐κB), and its transcriptional targets in the development and progression of many types of tumors. NF‐κB has been shown to drive the expression of proliferative (e.g. cyclin D), anti‐apoptotic (e.g. Bcl‐2), metastatic (e.g. cyclooxygenase 2) and pro‐angiogenic (e.g. ELR + CXC chemokines) genes, which unabated could contribute to tumorigenesis. Recently, the candidate tumor suppressor gene, ING4, was shown to interact with NF‐κB and to transcriptionally repress NF‐κB‐responsive genes. More importantly, ING4 expression has been shown to be downregulated in gliomas and head and neck squamous cell carcinomas. METHODS Here, we examined tumor biopsies from patients with either lung adenocarcinoma or lung squamous cell carcinoma (SCCA) and compared them to normal lung tissue biopsies from the same patients. RESULTS NF‐κB activation was elevated in the tumors compared to normal lung tissue, as were the ELR + CXC chemokines, CXCL1, CXCL5, and CXCL8. Interestingly, ING4 mRNA expression was significantly decreased in the tumor biopsies as compared to normal lung tissue. CONCLUSIONS These results highlight the importance of NF‐κB activity in tumor biology and implicate ING4 as a key regulator tumor development. Funded by NIH grants: CA87879, P5OCA90388 and HL67665.