title: Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer.
abstract: 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.
authors.affiliation: Department of Molecular Oncology, Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, New Delhi-110007, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Molecular Oncology, Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, New Delhi-110007, India.|Amity Institute of Molecular Medicine &Stem Cell Research (AIMMSCR), Amity University Campus, Uttar Pradesh, Sector-125, Noida-201313, India.
authors.forename: Prabhat
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Molecular Oncology, Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, New Delhi-110007, India.
authors.forename: Harsimrut
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Department of Otorhinolaryngology, Post Graduate Institute of Medical Education and Research, Dr. Ram Manohar Lohia (RML) Hospital, New Delhi-110010, India.
authors.forename: Nishi
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Molecular Oncology, Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, New Delhi-110007, India.
authors.forename: Daman
authors.initials: D
authors.lastname: Saluja
authors.affiliation: Division of Molecular Oncology, Institute of Cytology &Preventive Oncology (ICMR), Uttar Pradesh, Sector-39, Noida-201301, India.
authors.forename: Alok C
authors.initials: AC
authors.lastname: Bharti
authors.affiliation: Department of Molecular Oncology, Dr. B.R. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, New Delhi-110007, India.|Amity Institute of Molecular Medicine &Stem Cell Research (AIMMSCR), Amity University Campus, Uttar Pradesh, Sector-125, Noida-201313, India.
authors.forename: Bhudev C
authors.initials: BC
authors.lastname: Das
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D004247:DNA / Q000378:metabolism; D003710:Demography; D005260:Female; D051921:Fos-Related Antigen-2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D027383:Papillomaviridae / Q000502:physiology; D010641:Phenotype; D011379:Prognosis; D011485:Protein Binding; D055503:Protein Multimerization; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D015854:Up-Regulation
chemical_list: C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D004247:DNA