Implications of tyrosine phosphoproteomics in cervical carcinogenesis

Bernice L. Robinson-Bennett, James DeFord, Concepcion Diaz-Arrastia, Lyuba Levine, Hui Qui Wang, Edward V. Hannigan, John Papaconstantinou

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Worldwide cervical cancer remains a leading cause of mortality from gynecologic malignancies. The link between cervical cancer and persistent infection with HPV has been established. At a molecular level little is known about the transition from the precancerous state to invasive cancer. To elucidate this process, cervical biopsies from human specimens were obtained from precancerous state to stage III disease. Methods: Cervical biopsies were obtained from patients with a diagnosis of cervical cancer undergoing definitive surgery or staging operation. Biopsies were obtained from patients with precancerous lesions at the time of their excisional procedure. Control samples were obtained from patients undergoing hysterectomy for benign conditions such as fibroids. Samples were subjected to proteomic profiling using two dimensional gel electrophoresis with subsequent trypsin digestion followed by MALDI-TOF protein identification. Candidate proteins were then further studied using western blotting, immunoprecipitation and immunohistochemistry. Results: Annexin A1 and DNA-PKcs were found to be differentially expressed. Phosphorylated annexin A1 was up regulated in diseased states in comparison to control and its level was strongly detected in the serum of cervical cancer patients compared to controls. DNA-PKcs was noted to be hyperphosphorylated and fragmented in cancer when compared to controls. By immunohistochemistry annexin A1 was noted in the vascular environment in cancer and certain precancerous samples. Conclusion: This study suggests a probable role for protein tyrosine phosphorylation in cervical carcinogenesis. Annexin A1 and DNA-PK cs may have synergistic effects with HPV infection. Precancerous lesions that may progress to cervical cancer may be differentiated from lesions that will not base on similar immunohistochemical profile to invasive squamous cell carcinoma.

Original languageEnglish (US)
Article number2
JournalJournal of Carcinogenesis
Volume7
DOIs
StatePublished - Jul 17 2008

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Annexin A1
Uterine Cervical Neoplasms
Tyrosine
Biopsy
Carcinogenesis
DNA
Neoplasms
Phosphorylation
Proteins
Immunohistochemistry
Electrophoresis
Trypsin
Surgery
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Electrophoresis, Gel, Two-Dimensional
Leiomyoma
Infection
Hysterectomy
Immunoprecipitation
Gels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)
  • Cancer Research

Cite this

Robinson-Bennett, B. L., DeFord, J., Diaz-Arrastia, C., Levine, L., Wang, H. Q., Hannigan, E. V., & Papaconstantinou, J. (2008). Implications of tyrosine phosphoproteomics in cervical carcinogenesis. Journal of Carcinogenesis, 7, [2]. https://doi.org/10.1186/1477-3163-7-2

Implications of tyrosine phosphoproteomics in cervical carcinogenesis. / Robinson-Bennett, Bernice L.; DeFord, James; Diaz-Arrastia, Concepcion; Levine, Lyuba; Wang, Hui Qui; Hannigan, Edward V.; Papaconstantinou, John.

In: Journal of Carcinogenesis, Vol. 7, 2, 17.07.2008.

Research output: Contribution to journalArticle

Robinson-Bennett, BL, DeFord, J, Diaz-Arrastia, C, Levine, L, Wang, HQ, Hannigan, EV & Papaconstantinou, J 2008, 'Implications of tyrosine phosphoproteomics in cervical carcinogenesis', Journal of Carcinogenesis, vol. 7, 2. https://doi.org/10.1186/1477-3163-7-2
Robinson-Bennett BL, DeFord J, Diaz-Arrastia C, Levine L, Wang HQ, Hannigan EV et al. Implications of tyrosine phosphoproteomics in cervical carcinogenesis. Journal of Carcinogenesis. 2008 Jul 17;7. 2. https://doi.org/10.1186/1477-3163-7-2
Robinson-Bennett, Bernice L. ; DeFord, James ; Diaz-Arrastia, Concepcion ; Levine, Lyuba ; Wang, Hui Qui ; Hannigan, Edward V. ; Papaconstantinou, John. / Implications of tyrosine phosphoproteomics in cervical carcinogenesis. In: Journal of Carcinogenesis. 2008 ; Vol. 7.
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