Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA)

Nicol, Alcina F.; Pires, Andrea; Souza, Simone Rabello de; Nuovo, Gerard J.; Grinsztejn, Beatriz; Tristão, Aparecida; Russomano, Fábio Bastos; Velasque, Luciane; Silva, José Roberto Lapa e; Pirmez, Claude

doi:10.1186/1471-2407-8-289

Cited by 23 publications

(28 citation statements)

References 25 publications

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“…While staining intensity clearly decreased with disease severity, the proportion of positively stained cells remained high in all epithelia (above 40%) with the exception of normal endocervical cores (24%). As expected, Elf-1 was localized to both the cytoplasm and nucleus (13).…”

Section: Hpygo2 Protein Is Overexpressed In Cin3 and Sccmentioning

confidence: 63%

“…The bulk of research examining the role of Elf-1 in cancer has focused on the expression of Elf-1 in relation to other biomarkers, such as VEGF and PCNA or with clinical correlates. Detailed studies of Elf-1 gene targets in cancer include Elf-1 activation of TIE2 (46) and binding to the HCCS1 promoter (13). An efficient way to potentially identify all Elf-1 gene targets in these cells would be to conduct a genome-wide chromatin association analysis and to functionally group these genes to identify in which processes Elf-1 is involved.…”

Section: Discussionmentioning

confidence: 99%

“…ETS factors have well-established roles in carcinogenesis, regulating oncogenes and tumor suppressors involved in apoptosis, angiogenesis, invasion, and metastasis (8). Elf-1 itself activates genes involved in tumorigenesis (9)(10)(11)(12), is overexpressed in several cancers (13)(14)(15)(16), and correlates with poor prognosis (17)(18)(19)(20). In normal resting T lymphocytes, the pocket region of the Retinoblastoma (Rb) tumor suppressor interacts with the N-terminal LXCXE motif of promoter bound Elf-1 and blocks its transactivation (21).…”

Section: Introductionmentioning

confidence: 99%

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Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

Tzenov

Andrews

Voisey

et al. 2013

Molecular Cancer Research

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The human papillomavirus (HPV) is the etiologic agent of cervical cancer. In this study, we provide evidence for the human Pygopus (hPygo)2 gene as a cellular biomarker for HPV-related disease. In a tumor microarray of cervical cancer progression, hPygo2 levels were greater in high-grade lesions and squamous cell carcinomas than in normal epithelia. Similarly, hPygo2 mRNA and protein levels were greater in HPV-positive cervical cancer cells relative to uninfected primary cells. RNA interference (RNAi)-mediated depletion of HPV-E7 increased whereas E74-like factor (Elf)-1 RNAi decreased association of Retinoblastoma (Rb) tumor suppressor with the hPygo2 promoter in cervical cancer cell lines. Transfection of dominant-active Rb inhibited Elf-1-dependent activation of hPygo2, whereas Elf-1 itself increased hPygo2 expression. Chromatin immunoprecipitation assays showed that Rb repressed hPygo2 by inhibiting Elf-1 at the Ets-binding site in the hPygo2 promoter. These results suggested that abrogation of Rb by E7 resulted in derepression of Elf-1, which in turn stimulated expression of hPygo2.

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Section: Hpygo2 Protein Is Overexpressed In Cin3 and Sccmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

Tzenov

Andrews

Voisey

et al. 2013

Molecular Cancer Research

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“…The ETS family member ELF1 binds to the Pd, but its functional role in Pd transcription is not known (Rao et al 2002a). Interestingly, ELF1 upregulation has been associated with gynecological cancers of the cervix, uterus, and breast (Andrews et al 2008, Nicol et al 2008), but whether it has a role in ovarian tumors has not been determined. It will also be important to determine whether the Pd minimal element drives Rhox5 expression in cell types besides primary granulosa cells and tumor cells.…”

Section: The Pdmentioning

confidence: 99%

The Rhox genes

MacLean¹,

Wilkinson²

2010

Reproduction

103

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Homeobox genes encode transcription factors that have crucial roles in embryogenesis. A recently discovered set of homeobox genes -the Rhox genes -are expressed during both embryogenesis and in adult reproductive tissues. The 33 known mouse Rhox genes are clustered together in a single region on the X chromosome, while likely descendents of the primodial Rhox cluster, Arx and Esx1, have moved to other positions on the X chromosome. Here, we summarize what is known about the regulation and function of Rhox cluster and Rhox-related genes during embryogenesis and gametogenesis. The founding member of the Rhox gene cluster -Rhox5 (previously known as Pem) -has been studied in the most depth and thus is the focus of this review. We also discuss the unusually rapid evolution of the Rhox gene cluster.

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“…Aparentemente, as modificações pré-neoplásicas e neoplásicas acontecem por sua ação direta nas células basais do epitélio pluriestratificado, interferindo na atividade celular, promovendo alterações numéricas e estruturais dos cromossomos 3 . A instabilidade cromossômica, na aneuploidia seria um dos principais eventos associados ao processo carcinogenético 4 . A possível ação genotóxica do HPV e a incapacidade em depurar de maneira satisfatória o vírus podem ser caracterizadas clinicamente pela maior prevalência de alguns tipos específicos de tumores na população com comprometimento imunitário [5][6][7] .…”

Section: Introductionunclassified

Micronúcleos em células do colo uterino em mulheres HIV+ segundo sua condição de imunidade

Mendes¹,

Filho²,

Furoni³

et al. 2011

Rev. Bras. Ginecol. Obstet.

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PURPOSE: to investigate the micronucleation (MN) of exfoliated cells from the uterine cervix of HIV+ women according to immunocompetence status. We investigated the clinical conditions of immunocompetence by analyzing the levels of CD4+ lymphocytes and viral count for HIV (VC). METHODS: biological material was collected from 23 HIV+ patients whose cervical oncologic cytology results were negative. They were patients from the STD/AIDS-FCMS-PUCSP who underwent a cytobrush collection in the squamous columnar junction. Similar material was obtained from 19 healthy control women. The material, about 2000 cells per patient, was processed for cytology using light microscopy and an immersion objective. To analyze the immunological status of HIV+ patients we used CD4+ count and VC. Statistical analysis was performed using the χ 2 and Kolmorogov-Smirnov tests. RESULTS: twenty-three pacients composed the group of HIV+ women and 19 composed the control group. We found micronuclei (MN) in all HIV+ patients and in 84.2% of the control group. In 17 73.9% of the HIV+ patients and in 5.2% of the control group we found more than 7 MN cells. MN tended to occur more among women with poorer immunological status in the HIV+ group. CONCLUSIONS: HIV+ patients in the AIDS phase have a higher prevalence of micronucleated cells, as opposed to a control group. Also, the frequency of MN was associated with worse conditions of immunosuppression.

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Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA)

Abstract: Background: The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women.

Cited by 23 publications

References 25 publications

Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer

The Rhox genes

Micronúcleos em células do colo uterino em mulheres HIV+ segundo sua condição de imunidade

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