Transcription factor AP-1 in esophageal squamous cell carcinoma: alterations in activity and expression during human Papillomavirus infection.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir (J&K) region of India. A substantial proportion of esophageal carcinoma is associated with infection of high-risk HPV type 16 and HPV18, the oncogenic expression of which is controlled by host cell transcription factor Activator Protein-1 (AP-1). We, therefore, have investigated the role of DNA binding and expression pattern of AP-1 in esophageal cancer with or without HPV infection.


METHODS
Seventy five histopathologically-confirmed esophageal cancer and an equal number of corresponding adjacent normal tissue biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and expression of AP-1 family of proteins by PCR, gel shift assay and immunoblotting respectively.


RESULTS
A high DNA binding activity and elevated expression of AP-1 proteins were observed in esophageal cancer, which differed between HPV positive (19%) and HPV negative (81%) carcinomas. While JunB, c-Fos and Fra-1 were the major contributors to AP-1 binding activity in HPV negative cases, Fra-1 was completely absent in HPV16 positive cancers. Comparison of AP-1 family proteins demonstrated high expression of JunD and c-Fos in HPV positive tumors, but interestingly, Fra-1 expression was extremely low or nil in these tumor tissues.


CONCLUSIONS
Differential AP-1 binding activity and expression of its specific proteins between HPV--positive and HPV--negative cases indicate that AP-1 may play an important role during HPV-induced esophageal carcinogenesis.
Hussain
Showket
S
Division of Molecular Oncology, Institute of Cytology & Preventive Oncology (ICMR), Noida, India. shussain1712@yahoo.co.in
Bharti
Alok C
AC
Salam
Irfana
I
Bhat
Mohammad Akbar
MA
Mir
Mohammad Muzaffar
MM
Hedau
Suresh
S
Siddiqi
Mushtaq A
MA
Basir
Seemi Farhat
SF
Das
Bhudev C
BC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
D018808:Transcription Factor AP-1