ArticleOncogene2006
Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data.BMC cancer · 2007Pooled it
- Computer Image Analysis Reveals C-Myc as a Potential Biomarker for Discriminating between Keratoacanthoma and Cutaneous Squamous Cell Carcinoma.BioMed research international · 2022Article
- Organotypic Co-Cultures as a Novel 3D Model for Head and Neck Squamous Cell Carcinoma.Cancers · 2020Article
- T-lymphocyte profiles differ between keratoacanthomas and invasive squamous cell carcinomas of the human skin.Cancer immunology, immunotherapy : CII · 2018Article
- Isorhapontigenin suppresses growth of patient-derived glioblastoma spheres through regulating miR-145/SOX2/cyclin D1 axis.Neuro-oncology · 2016Article
- Epidermal Differentiation Complex: A Review on Its Epigenetic Regulation and Potential Drug Targets.Cell journal · 2016Review
- The telomere profile distinguishes two classes of genetically distinct cutaneous squamous cell carcinomas.Oncogene · 2014Article
- Cyclin d1 downregulation contributes to anticancer effect of isorhapontigenin on human bladder cancer cells.Molecular cancer therapeutics · 2013Article
- Peripheral T-cell Lymphoma with Cyclin D1 overexpression: a case report.Diagnostic pathology · 2012Article
- A decisive function of transforming growth factor-β/Smad signaling in tissue morphogenesis and differentiation of human HaCaT keratinocytes.Molecular biology of the cell · 2011Article
- Squamous Cell Carcinoma - Similarities and Differences among Anatomical Sites.American journal of cancer research · 2011Article
- Cyclin D1 and cyclin D-dependent kinases enhance oral keratinocyte proliferation but do not block keratinocyte differentiation.International journal of oncology · 2010Article
- Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck squamous cell carcinoma.International journal of cancer · 2009Article
- PI3K/Akt/JNK/c-Jun signaling pathway is a mediator for arsenite-induced cyclin D1 expression and cell growth in human bronchial epithelial cells.Current cancer drug targets · 2009Article
- Stromal control of oncogenic traits expressed in response to the overexpression of GLI2, a pleiotropic oncogene.Oncogene · 2009Article
- Cyclin D1 downregulation is important for permanent cell cycle exit and initiation of differentiation induced by anchorage-deprivation in human keratinocytes.Journal of cellular biochemistry · 2009Article
- UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes.Oncogene · 2008Article
- Cortactin expression predicts poor survival in laryngeal carcinoma.British journal of cancer · 2008Article
- Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character.Oncogene · 2008Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immune-suppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic co-cultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.
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