Ras and C-Myc Oncoproteins during Tumor Progression in the Uterine Cervix

Nair, S. Asha; Nair, M. Balaraman; Jayaprakash, P. G.; Rajalekshmy, T. N.; Nair, Muralidharan; Pillai, M. Radhakrishna

doi:10.1177/030089169808400514

Cited by 19 publications

(16 citation statements)

References 18 publications

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“…NF-kB may be activated by cytokines, by alterations in epidermal growth factor or receptor expression, Ras activation, or through cell damage and changes in the oxidation-reduction state (Karin et al, 2002). Increased immunoreactivity for Nras was evident in the basaloid cells of malignant cervical lesions, with the maximum value of 66% found in PDSCC (Nair et al, 1998). A significant percentage (24.2%) of early-stage cervical cancers contain activated Ras (Grendys et al, 1997).…”

Section: Nf-jb Activation In Cervical Cancermentioning

confidence: 99%

NF-κB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix

et al. 2003

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We demonstrate, for the first time, that the transcription factor NF-jB is constitutively activated during human cervical cancer progression. Immunohistochemical analysis was done using 106 paraffin-embedded cervical tissue specimens of different histological grades. In normal cervical tissue and low-grade squamous intraepithelial lesions, p50, RelA and IjB-a were mainly localized in the cytosol, whereas in high-grade lesions and squamous cell carcinomas, p50-RelA heterodimers translocated into the nucleus with a concurrent decrease in IjB-a protein. By Western blot analysis, p50 and RelA were detectable mainly in the cytosolic and nuclear extracts in normal and cancer tissues, respectively, and cytosolic IjB-a expression was detectable in normal but not in cancer cervical tissues. NF-jB DNA-binding activity increased during cervical cancer progression and the binding complex was mainly composed of the p50-RelA heterodimers as revealed by electrophoretic mobility shift assays. Semiquantitative RT-PCR analysis, however, showed increased levels of IjB-a mRNA in cancer samples presumably because of feedback regulation as a result of enhanced NF-jB DNA-binding activity and a consequent functional activation of NF-jB. Further immunohistochemical analysis with an antibody to phospho IjB-a revealed that phosphorylation occurs mainly in squamous intraepithelial lesions, suggesting that the IjB-a gets phosphorylated initially and degraded as the tumor progressed.

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Section: Nf-jb Activation In Cervical Cancermentioning

confidence: 99%

NF-κB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix

et al. 2003

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“…11 Chlamydia trachomatis and HPV high-risk types may contribute to neoplastic changes in the transformation of the uterine cervix and also might modulate expression of c-myc oncogene. 12 …”

Section: Introductionmentioning

confidence: 99%

Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions

Protrka¹,

Arsenijevic²,

Dimitrijević³

et al. 2011

Eur J Histochem

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To establish the role of co-overexpression of bcl-2 and c-myc protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL), high grade SIL, portio vaginalis uteri (PVU) carcinoma in situ and PVU invasive carcinoma, stage IA-IIA (study group) and 36 samples without SIL or malignancy (control group). The expression of bcl-2 and c-myc was detected immunohistochemically using a monoclonal antibody. Fisher's exact test (P<0.05) was used to assess statistical significance. Overexpression of bcl-2 was found to increase in direct relation to the grade of the cervical lesions. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be said that in patients with bcl-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. Co-overexpression of bcl-2 and c-myc oncogenes was found only in patients with PVU invasive carcinoma (6/26-23.0%). Statistically significant difference was not found in the frequency of co-overexpression in patients with PVU invasive carcinoma in relation to the control group (Fisher's test; P=0.064). The method's sensitivity of determining these oncogenes with the aim of detecting PVU invasive carcinoma was 23%, while specificity was 72.2%. On the basis of high predictive values (100%), speaking in statistical terms, it can be concluded that all patients with co-overexpression of bcl-2 and c-myc oncogenes will have PVU invasive carcinoma. We confirmed in our research that co-overexpression of bcl-2 and c-myc oncogenes was increased only in PVU invasive carcinoma. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of bcl-2 and c-myc co-overexpression in cervical carcinogenesis.

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“…64,65 However, the natural history of high-grade CIN may be potentially be related to an increased expression of cellular oncogenes, including ras and c-myc oncoproteins. 66 Consistent with this, AAV have been shown to inhibit cellular oncogenes (c-H-ras, c-fos, c-myc). 67 Furthermore, previous studies suggest that coinfection with AAV and HPV may induce cytopathic effects, preventing the respective cells from surviving.…”

Section: Discussionmentioning

confidence: 70%

Adeno‐associated virus seropositivity and HPV‐induced cervical cancer in Spain and Colombia

et al. 2001

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Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinicbased controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5؉/6؉ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1-0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1-1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3-6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix.

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Ras and C-Myc Oncoproteins during Tumor Progression in the Uterine Cervix

Abstract: These results therefore suggest that c-myc and N-ras oncoproteins are important during tumor progression in the uterine cervix.

Cited by 19 publications

References 18 publications

NF-κB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix

NF-κB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix

Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions

Adeno‐associated virus seropositivity and HPV‐induced cervical cancer in Spain and Colombia

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