CoChat
Sign Up
Cited by 145

The DOI matches its Crossref record.

Human Papillomavirus Type 16 E7 Up-regulates AKT Activity through the Retinoblastoma Protein

Menges, Craig W., Baglia, Laurel A., Lapoint, Randi, McCance, Dennis J.·2006·Cancer Research
DOI 10.1158/0008-5472.can-06-0499
Open this paper in CoChat — free account

Abstract

Human papillomaviruses (HPV) are small DNA tumor viruses causally associated with cervical cancer. The early gene product E7 from high-risk HPV is considered the major transforming protein expressed by the virus. Although many functions have been described for E7 in disrupting normal cellular processes, we describe in this study a new cellular target in primary human foreskin keratinocytes (HFK), the serine/threonine kinase AKT. Expression of HPV type 16 E7 in HFK caused inhibition of differentiation, hyperproliferation, and up-regulation of AKT activity in organotypic raft cultures. The ability of E7 to up-regulate AKT activity is dependent on its ability to bind to and inactivate the retinoblastoma (Rb) gene product family of proteins. Furthermore, we show that knocking down Rb alone, with short hairpin RNAs, was sufficient to up-regulate AKT activity in differentiated keratinocytes. Up-regulation of AKT activity and loss of Rb was also observed in HPV-positive cervical high-grade squamous intraepithelial lesions when compared with normal cervical tissue. Together, these data provide evidence linking inactivation of Rb by E7 in the up-regulation of AKT activity during cervical cancer progression. (Cancer Res 2006; 66(11): 5555-9)

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-06-0499

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 18

  1. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189: 12–9. · DOI
  2. McMurray HR, Nguyen D, Westbrook TF, McAnce DJ. Biology of human papillomaviruses. Int J Exp Pathol 2001; 82: 15–33. · DOI
  3. Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene 2005; 24: 7455–64. · DOI
  4. Brazil DP, Park J, Hemmings BA. PKB binding proteins. Getting in on the Akt. Cell 2002; 111: 293–303. · DOI
  5. Pim D, Massimi P, Dilworth SM, Banks L. Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A. Oncogene 2005; 24: 7830–8. · DOI · Paper page
  6. Westbrook TF, Nguyen DX, Thrash BR, McCance DJ. E7 abolishes raf-induced arrest via mislocalization of p21(Cip1). Mol Cell Biol 2002; 22: 7041–52. · DOI
  7. Guess JC, McCance DJ. Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3α production. J Virol 2005; 79: 14852–62. · DOI
  8. Incassati A, Patel D, McCance DJ. Induction of tetra-ploidy through loss of p53 and upregulation of Plk1 by human papillomavirus type-16 E6. Oncogene 2006; 25: 2444–51. · DOI
  9. Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 1975; 6: 331–43. · DOI
  10. McCance DJ, Kopan R, Fuchs E, Laimins LA. Human papillomavirus type 16 alters human epithelial cell differentiation in vitro. Proc Natl Acad Sci U S A 1988; 85: 7169–73. · DOI · Paper page
  11. Nguyen DX, Westbrook TF, McCance DJ. Human papillomavirus type 16 E7 maintains elevated levels of the cdc25A tyrosine phosphatase during deregulation of cell cycle arrest. J Virol 2002; 76: 619–32. · DOI · Paper page
  12. Altomare DA, You H, Xiao GH, et al. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene 2005; 24: 6080–9. · DOI
  13. Hill R, Song Y, Cardiff RD, Van Dyke T. Heterogeneous tumor evolution initiated by loss of pRb function in a preclinical prostate cancer model. Cancer Res 2005; 65: 10243–54. · DOI
  14. Fiedler M, Muller-Holzner E, Viertler HP, et al. High level HPV-16 E7 oncoprotein expression correlates with reduced pRb-levels in cervical biopsies. FASEB J 2004; 18: 1120–2. · DOI
  15. Calautti E, Li J, Saoncella S, Brissette JL, Goetinck PF. Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus death. J Biol Chem 2005; 280: 32856–65. · DOI
  16. Janes SM, Ofstad TA, Campbell DH, Watt FM, Prowse DM. Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt. J Cell Sci 2004; 117: 4157–68. · DOI
  17. Chaussepied M, Ginsberg D. Transcriptional regulation of AKT activation by E2F. Mol Cell 2004; 16: 831–7. · DOI
  18. Bertelsen BI, Steine SJ, Sandvei R, Molven A, Laerum OD. Molecular analysis of the PI3K-AKT pathway in uterine cervical neoplasia: Frequent PIK3CA amplification and AKT phosphorylation. Int J Cancer 2006; 118: 1877–83. · DOI

Cited by

Metadata

Authors
Menges, C. W., Baglia, L. A., Lapoint, R., & McCance, D. J.
Affiliations
  • 1Biochemistry and Biophysics, Departments of
  • 2Microbiology and Immunology, and
  • 3Pathology and Laboratory Medicine and
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2006-06-01
Volume
66
Issue
11
Pages
5555-5559
ISSN
  • 0008-5472
  • 1538-7445
DOI
10.1158/0008-5472.can-06-0499
Cited by
145
References
0
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review