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.



Disease Annotations    

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