RGD Reference Report - Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer. - Rat Genome Database

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Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer.

Authors: Gupta, S  Kumar, P  Kaur, H  Sharma, N  Saluja, D  Bharti, AC  Das, BC 
Citation: Gupta S, etal., Sci Rep. 2015 Nov 19;5:16811. doi: 10.1038/srep16811.
RGD ID: 11535375
Pubmed: PMID:26581505   (View Abstract at PubMed)
PMCID: PMC4652185   (View Article at PubMed Central)
DOI: DOI:10.1038/srep16811   (Journal Full-text)

Tongue squamous cell carcinoma (TSCC) is most aggressive head and neck cancer often associated with HR-HPV infection. The role of AP-1 which is an essential regulator of HPV oncogene expression and tumorigenesis is not reported in tongue cancer. One hundred tongue tissue biopsies comprising precancer, cancer and adjacent controls including two tongue cancer cell lines were employed to study the role of HPV infection and AP-1 family proteins. An exclusive prevalence (28%) of HR-HPV type 16 was observed mainly in well differentiated tongue carcinomas (78.5%). A higher expression and DNA binding activity of AP-1 was observed in tongue tumors and cancer cell lines with c-Fos and Fra-2 as the major binding partners forming the functional AP-1 complex but c-Jun participated only in HPV negative and poorly differentiated carcinoma. Knocking down of Fra-2 responsible for aggressive tongue tumorigenesis led to significant reduction in c-Fos, c-Jun, MMP-9 and HPVE6/E7 expression but Fra-1 and p53 were upregulated. The binding and expression of c-Fos/Fra-2 increased as a function of severity of tongue lesions, yet selective participation of c-Jun appears to promote poor differentiation and aggressive tumorigenesis only in HPV negative cases while HPV infection leads to well differentiation and better prognosis preferably in nonsmokers.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tongue squamous cell carcinoma  IEP 11535375; 11535375; 11535375; 11535375; 11535375; 11535375protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOBCL2 (Homo sapiens)11535375; 11535375protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOCCND1 (Homo sapiens)11535375; 11535375protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  IEP 11535375; 11535375; 11535375mRNA and protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  IEP 11535375protein:decreased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOFOS (Homo sapiens)11535375; 11535375mRNA and protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOFOSB (Homo sapiens)11535375; 11535375protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOFOSL1 (Homo sapiens)11535375; 11535375protein:decreased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOFOSL2 (Homo sapiens)11535375; 11535375mRNA and protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOJUN (Homo sapiens)11535375; 11535375mRNA and protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOJUNB (Homo sapiens)11535375; 11535375protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOJUND (Homo sapiens)11535375; 11535375protein:increased expression:tongue (human)RGD 
tongue squamous cell carcinoma  ISOMMP9 (Homo sapiens)11535375; 11535375protein:increased expression:tongue (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcl2  (BCL2, apoptosis regulator)
Ccnd1  (cyclin D1)
Fos  (Fos proto-oncogene, AP-1 transcription factor subunit)
Fosb  (FosB proto-oncogene, AP-1 transcription factor subunit)
Fosl1  (FOS like 1, AP-1 transcription factor subunit)
Fosl2  (FOS like 2, AP-1 transcription factor subunit)
Jun  (Jun proto-oncogene, AP-1 transcription factor subunit)
Junb  (JunB proto-oncogene, AP-1 transcription factor subunit)
Jund  (JunD proto-oncogene, AP-1 transcription factor subunit)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Bcl2  (B cell leukemia/lymphoma 2)
Ccnd1  (cyclin D1)
Fos  (FBJ osteosarcoma oncogene)
Fosb  (FBJ osteosarcoma oncogene B)
Fosl1  (fos-like antigen 1)
Fosl2  (fos-like antigen 2)
Jun  (jun proto-oncogene)
Junb  (jun B proto-oncogene)
Jund  (jun D proto-oncogene)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
BCL2  (BCL2 apoptosis regulator)
CCND1  (cyclin D1)
FOS  (Fos proto-oncogene, AP-1 transcription factor subunit)
FOSB  (FosB proto-oncogene, AP-1 transcription factor subunit)
FOSL1  (FOS like 1, AP-1 transcription factor subunit)
FOSL2  (FOS like 2, AP-1 transcription factor subunit)
JUN  (Jun proto-oncogene, AP-1 transcription factor subunit)
JUNB  (JunB proto-oncogene, AP-1 transcription factor subunit)
JUND  (JunD proto-oncogene, AP-1 transcription factor subunit)
MMP9  (matrix metallopeptidase 9)


Additional Information