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@ARTICLE{Vuckovic:278405,
      author       = {N. Vuckovic$^*$ and K. Hoppe-Seyler$^*$ and A. Riemer$^*$},
      title        = {{C}haracterization of {D}o{T}c2 4510-{I}dentifying {HPV}16
                      {P}resence in a {C}ervical {C}arcinoma {C}ell {L}ine
                      {P}reviously {C}onsidered to {B}e {HPV}-{N}egative.},
      journal      = {Cancers},
      volume       = {15},
      number       = {15},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-01639},
      pages        = {3810},
      year         = {2023},
      note         = {#EA:F130#LA:F130#},
      abstract     = {Cervical cancer is the fourth leading cause of cancer
                      deaths in women, with over 340,000 women dying from this
                      disease in 2020. Almost all cases have an underlying
                      persistent infection with an oncogenic high-risk type of
                      human papillomavirus (HPV), mainly HPV16. While cervical
                      squamous cell carcinoma is hardly ever HPV-negative, a small
                      subset of adenocarcinoma exhibits absence of HPV, even after
                      disproval of false-negative testing results due to low viral
                      load. This proportion is evident in many cervical cancer
                      studies and is reflected in the repertoire of model cell
                      lines commonly used in research. As the viral origin of
                      cervical cancer makes it a disease preventable and
                      potentially treatable by immunotherapeutic approaches, it is
                      the focus of many studies. For pertinent research, both a
                      broad set of HPV-infected cervical carcinoma models are
                      required, as well as stringent negative controls. A
                      ubiquitously used HPV-negative cervical adenocarcinoma cell
                      line is C-33A. Another cervical cancer cell line is
                      available for purchase from the American Type Culture
                      Collection (ATCC), namely DoTc2 4510, described to be
                      HPV-negative and thus as a model for a rare gynecological
                      malignancy. Here, we present findings proving that DoTc2
                      4510 is, in fact, an HPV16-positive cell line. This we
                      assessed using a highly sensitive nested multiplex PCR
                      protocol adapted for the identification of 12 carcinogenic
                      HPV types and a second PCR targeting the HPV16 oncogenes E6
                      and E7. Subsequently, the protein expression of E6 and E7
                      was examined, as well as the expression of their target
                      proteins p53, p21, and p16INK4a, to assess E6/E7
                      functionality. Finally, to attest to the survival dependence
                      of DoTc2 4510 cells on HPV16, we performed an HPV16
                      E6/E7-targeted siRNA knock-down, which indeed led to
                      senescence induction. Together, these findings demonstrate
                      that DoTc2 4510 is an HPV16-transformed cell line.},
      keywords     = {DoTc2 4510 (Other) / HPV (Other) / HPV-negative cervical
                      cancer (Other) / cell authentication (Other) / cervical
                      cancer (Other)},
      cin          = {F130 / F065},
      ddc          = {610},
      cid          = {I:(DE-He78)F130-20160331 / I:(DE-He78)F065-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37568626},
      pmc          = {pmc:PMC10417116},
      doi          = {10.3390/cancers15153810},
      url          = {https://inrepo02.dkfz.de/record/278405},
}