Expression of a Single, Viral Oncoprotein in Skin Epithelium Is Sufficient to Recruit Lymphocytes

Choyce, Allison; Yong, Michelle; Narayan, Sharmal; Mattarollo, Stephen R.; Liem, Amy; Lambert, Paul F.; Frazer, Ian H.; Leggatt, Graham R.
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Established cancers are frequently associated with a lymphocytic infiltrate that fails to clear the tumour mass. In contrast, the importance of recruited lymphocytes during premalignancy is less well understood. In a mouse model of premalignant skin epithelium, transgenic mice that express the human papillomavirus type 16 (HPV16) E7 oncoprotein under a keratin 14 promoter (K14E7 mice) display epidermal hyperplasia and have a predominant infiltrate of lymphocytes consisting of both CD4 and CD8 T cells. Activated, but not naïve T cells, were shown to preferentially traffic to hyperplastic skin with an increased frequency of proliferative CD8+ T cells and CD4+ T cells expressing CCR6 within the tissue. Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb) led to reduced epithelial hyperplasia and T cell infiltrate. Finally, while K14E7 donor skin grafts are readily accepted onto syngeneic, non-transgenic recipients, these same skin grafts lacking skin-resident lymphocytes were rejected. Our data suggests that expression of a single oncoprotein in the epidermis is sufficient for lymphocyte trafficking (including immunosuppressive lymphocytes) to premalignant skin.


Related Articles

  • Gene expression: Pancreas under scrutiny. Skipper, Magdalena // Nature Reviews Genetics;May2003, Vol. 4 Issue 5, p331 

    Discusses research being done on gene expression. Reference to a study by M.-K. Chiang and D.A. Melton, published in the April 2003 issue of 'Developmental Cell'; Method used to profile single cells that were isolated from an E10.5 mouse pancreatic epithelium.

  • MDM2 binding protein, a novel metastasis suppressor. Iwakuma, Tomoo; Agarwal, Neeraj // Cancer & Metastasis Reviews;Dec2012, Vol. 31 Issue 3/4, p633 

    MDM2 binding protein (MTBP) is a protein that interacts with oncoprotein murine double minute (MDM2), a major inhibitor of the tumor suppressor p53. Overexpression of MTBP leads to p53-independent cell proliferation arrest, which is in turn blocked by simultaneous overexpression of MDM2....

  • Hepatitis B virus X protein upregulates Lin28A/Lin28B through Sp-1/c-Myc to enhance the proliferation of hepatoma cells. You, X; Liu, F; Zhang, T; Lv, N; Liu, Q; Shan, C; Du, Y; Kong, G; Wang, T; Ye, L; Zhang, X // Oncogene;1/23/2014, Vol. 33 Issue 4, p449 

    Hepatitis B virus X protein (HBx) plays critical roles in the pathogenesis of hepatocellular carcinoma (HCC). Here, we were interested in knowing whether the oncogene Lin28A and its homolog Lin28B are involved in the hepatocarcinogenesis mediated by HBx. We showed that the expression levels of...

  • Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma. Reid, G.; Pel, M. E.; Kirschner, M. B.; Cheng, Y. Y.; Mugridge, N.; Weiss, J.; Williams, M.; Wright, C.; Edelman, J. J. B.; Vallely, M. P.; McCaughan, B. C.; Klebe, S.; Brahmbhatt, H.; MacDiarmid, J. A.; van Zandwijk, N. // Annals of Oncology;Dec2013, Vol. 24 Issue 12, p3128 

    Background Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches to therapy are needed. Reduced expression of miR-15/16 in a range of cancer types has suggested a tumour suppressor function for these microRNAs, and re-expression has been shown to inhibit tumour...

  • Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis. Pan, Yan; Zhong, Li-jun; Zhou, Hong; Wang, Xin; Chen, Kui; Yang, Hao-peng; Xiaokaiti, Yilixiati; Maimaiti, Aikebaier; Jiang, Ling; Li, Xue-jun // Acta Pharmacologica Sinica;Jun2012, Vol. 33 Issue 6, p798 

    Aim:To investigate the inhibitory effects of heparin on PC-3M cells proliferation in vitro and B16-F10-luc-G5 cells metastasis in Balb/c nude mice and identify the protein expression patterns to elucidate the action mechanism of heparin.Methods:Human prostate cancer PC-3M cells were incubated...

  • The Study of the Effect of Hedyotis diffusa on the Proliferation and the Apoptosis of the Cervical Tumor in Nude Mouse Model. Zhang, Peiying; Zhang, Bei; Gu, Juan; Hao, Lin; Hu, Fangfang; Han, Conghui // Cell Biochemistry & Biophysics;Jul2015, Vol. 72 Issue 3, p783 

    To study the inhibitory effect of Hedyotis diffusa on cervical cancer and its underlining biomolecular mechanism. Human cervical carcinoma nude mice xenograft was established and the mice were treated by intra-gastric administration of boiled and concentrated Hedyotis diffusa. When the tumor...

  • Effects of Cyclooxygenase Inhibitors in Combination with Taxol on Expression of Cyclin D1 and Ki-67 in a Xenograft Model of Ovarian Carcinoma. Wei Li; Jia-Hui Cai; Jun Zhang; Yun-Xian Tang; Liang Wan // International Journal of Molecular Sciences;Aug2012, Vol. 13 Issue 8, p9741 

    The present study was designed to investigate the effects of cyclooxygenase (COX) inhibitors in combination with taxol on the expression of cyclin D1 and Ki-67 in human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were treated with 100 mg/kg celecoxib (a COX-2 selective...

  • A Rac1/Cdc42 GTPase-Specific Small Molecule Inhibitor Suppresses Growth of Primary Human Prostate Cancer Xenografts and Prolongs Survival in Mice. Zins, Karin; Lucas, Trevor; Reichl, Patrick; Abraham, Dietmar; Aharinejad, Seyedhossein // PLoS ONE;Sep2013, Vol. 8 Issue 9, p1 

    Deregulated Rho GTPases Rac1 and Cdc42 have been discovered in various tumors, including prostate and Rac protein expression significantly increases in prostate cancer. The Rac and Cdc42 pathways promote the uncontrolled proliferation, invasion and metastatic properties of human cancer cells. We...

  • 14-3-3s and p63 play opposing roles in epidermal tumorigenesis. Li, Qiutang; Sambandam, Sumitha A.T.; Lu, Helen J.; Thomson, Alexander; Kim, Sung-hye; Lu, Huayi; Xin, Ying; Lu, Qingxian // Carcinogenesis;Dec2011, Vol. 32 Issue 12, p1782 

    14-3-3s plays a regulatory role in epidermal epithelial differentiation and loss of 14-3-3s leads to increased proliferation and impaired differentiation. A tumor suppressor function for 14-3-3s has been proposed based on the fact that some epithelial-derived tumors lose 14-3-3s expression. p63,...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics