Constitutive activation of transcription factor AP-1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and AP-1 activity in HeLa cells by curcumin

Abstract

The transcription factor AP-1 plays a central role in the transcriptional regulation of specific types of high-risk human papillomaviruses (HPVs) such as HPV16 and HPV18, which are etiologically associated with the development of cancer of the uterine cervix in women. In our study, we investigated the AP-1 binding activity and the expression pattern of different members of the AP-1 transcription factor family (c-Jun, JunB, JunD, c-Fos, FosB, Fra-1 and Fra-2) in different grades of cervical lesions starting from mild dysplasia to invasive cervical tumors, including normal control tissues, using specific antibodies raised against each of the AP-1 members. Results indicate that though AP-1 showed high binding activity and the majority of its members were highly expressed in tumor tissues, there is a distinct pattern of gradual increase of c-fos and a concomitant decrease of fra-1 expression that perfectly match the progression of cervical lesions. While c-fos is highly expressed in invasive cervical tumor, the expression of fra-1 becomes almost nil or absent, but the reverse is true in both controls and early precancerous lesions. These findings corroborate the results obtained in the cervical cancer cell line, HeLa.

Selective Suppression of NF-kBp65 in Hepatitis Virus-Infected Pregnant Women Manifesting Severe Liver Damage and High Mortality

“…Frozen liver biopsies were minced finely and immediately processed for preparation of nuclear extract using previously described methods (19). The blood samples collected were also immediately processed for nuclear extract preparation using the same protocol as for tissue biopsies but with the exception that peripheral blood mononuclear cells (PBMCs) were first separated from whole blood using Histopaq solution (Sigma, St. Louis, MO, USA) and then processed for protein extraction.…”

“…The blood samples collected were also immediately processed for nuclear extract preparation using the same protocol as for tissue biopsies but with the exception that peripheral blood mononuclear cells (PBMCs) were first separated from whole blood using Histopaq solution (Sigma, St. Louis, MO, USA) and then processed for protein extraction. Western blot analysis was carried out as described earlier (19,20). The bands were visualized with an anti-rabbit IgG antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) conjugated with horseradish peroxidase in a dilution of 1:10000, using the Santa Cruz Luminol detection kit.…”

“…Electrophoretic mobility shift assay (EMSA) was carried out using previously described techniques (19). For EMSA, the following oligonucleotides were used: an NF-kB consensus sequence 5′-AGTTGAGGGGACTTTCCCAGGC-3′ and an Oct-1 consensus oligonucleotide primer 5′-TGTCGAATGCAAATCACTA-GAA-3′.…”

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

“…In osteosarcoma and endometrial carcinoma, c-Fos overexpression was associated with high-grade lesions and adverse outcome (Gamberi et al, 1998;Bamberger et al, 2001). In a comparative analysis between precancerous lesion of the cervix uteri and invasive cervical cancer, c-Fos expression was significantly lower in precancerous lesions (Prusty and Das, 2005). C-Fos has also been identified as independent predictor of decreased survival in breast cancer (Bland et al, 1995).…”

The Activator Protein-1 Transcription Factor in Respiratory Epithelium Carcinogenesis

“…Some tumor-preventing agents function by deregulating Fra-1 expression in model systems (e.g., curcumin; ref. 114). Yet, most data concerning the function of Fra-1 in respiratory epithelium carcinogenesis are based on experimental results, and the role of these transcription factors in clinical tumors is still obscure (110).…”