Cytokeratins (CK) are members of intermediate filaments, which are predominantly found in epithelial cells. Different types of epithelia are characterized by a distinct composition of CK. Recently immunohistochemical investigations demonstrated that, among others, CKs 6, 14, 16 and 17 are regularly expressed in benign stratified squamous epithelium of the head and neck as well as in squamous cell carcinoma of the head and neck (HNSCC) in contrast to CKs 1, 10 and 11, that were only rarely expressed in these tissues.
Total RNA was isolated from 15 primary cell lines derived from HNSCC and from 15 tissue samples of oro- and hypopharyngeal carcinomas obtained from surgery specimens. CK expression was evaluated by RT-PCR, Western blot analysis and immunohistochemistry.
CK6 and 16 were found to be expressed in both groups at almost 100%. The expression level of CK14 remained constant (73%) in both groups, at the RNA and protein level. CK17 was more frequently present in tumour specimens than in HNSCC cell lines. The immunohistochemical results of the surgical tumour specimens confirmed the results of Western blot analysis.
The presented results show high and stable expression rates for CK6 and CK16 in HNSCC. These results will serve as a basis for further investigations concerning the search for circulating tumour cells and micrometastases. In addition, we found that cytokeratin expression in HNSCC is different on the RNA level compared to the protein level.
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"A recent report associates keratin 6a expression with urothelial cell proliferation and wound repair (Sun 2006). Keratin 6a has been found to be overexpressed in the overlying epidermis of patients with dermatofibromas (Stoler et al. 1989), in keratinizing and nonkeratinizing squamous cell carcinomas of the cervix (Smedts et al. 1992), and in squamous cell carcinomas of the head and neck (Sesterhenn et al. 2005). To our knowledge keratin 6a has not been examined in human bladder cancer. "
[Show abstract][Hide abstract] ABSTRACT: Cadmium and arsenite can directly and malignantly transform the UROtsa cell line. The tumor heterotransplants produced from these transformed cells have histologic features consistent with human bladder cancer. Previous microarray analysis of total RNA from the parental and transformed cells suggested that keratin 6a was overexpressed as a result of cell transformation.
Our goals were to verify overexpression of keratin 6a in Cd(2+)- and As(3+)-transformed UROtsa cells, the corresponding tumor heterotransplants, and human bladder cancer biopsy specimens and to assess what factors may be involved in keratin 6a overexpression.
Expression was assessed with real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. We used the effect of addition and deletion of potential growth factors in the cell culture growth medium to assess possible pathways used in keratin 6a overexpression.
Cd(2+)- and As(3+)-transformed cells grown in serum-containing growth medium, as well as the derived tumor heterotransplants, overexpressed keratin 6a mRNA and protein compared with UROtsa cells grown in serum-containing growth medium. Immunostaining of keratin 6a in tumor heterotransplants showed focal staining of the tumor cells that was localized to the cytoplasm. Focal immunostaining of keratin 6a was also found in some but not all archival patient specimens of high-grade bladder cancer, confirming translation of the results to human bladder cancer. Studies on growth factor deletion and addition indicated that the level of keratin 6a expression was regulated by the presence of both insulin and epidermal growth factor (EGF). In contrast, growth factors had no effect on the elevated levels of keratin 6a expression found in transformed UROtsa cells.
Our present studies suggest that keratin 6a expression may be a biomarker for malignant urothelial cells that possess an activated EGF and or insulin growth factor pathway.
Preview · Article · May 2008 · Environmental Health Perspectives
[Show abstract][Hide abstract] ABSTRACT: The presence of tumor cells in the bone marrow of primary breast cancer patients at surgery has been shown to be an independent prognostic indicator of relapse. Tumor cells have been detected either directly, using immunocytochemical staining, or indirectly, using reverse transcription-polymerase chain reaction (RT-PCR). Studies have been initiated to determine whether the presence of disseminated cells can be monitored during the therapy of patients with primary breast cancer, and thus potentially be used to predict relapse before overt metastases are detectable. Studies are also ongoing to improve methods of detection, such as immunobead enrichment followed by staining and real-time RT-PCR, and to find alternative markers for the disseminated cells. Studies of patients with overt metastases have shown that there is a large tumor load in the peripheral blood and that this predicts overall survival. This article reviews the published literature on studies carried out in both primary and metastatic breast cancer patients, the methodologies and markers used, and improvements in detection methodologies that are being investigated including real-time RT-PCR, novel markers, enrichment and automated image analysis.
No preview · Article · Feb 2007 · Nature Clinical Practice Oncology
[Show abstract][Hide abstract] ABSTRACT: Little is known about the genetic background of keratocystic odontogenic tumors (KCOT, odontogenic keratocysts). Our aim was to characterize genomic aberrations in sporadic KCOT using cDNA-expression arrays and array-comparative genomic hybridization. For cDNA-expression arrays, 10 KCOT specimens and 20 fetal tooth germs were studied. Quantitative real-time reverse-transcription/polymerase chain-reaction and immunohistochemical studies were also undertaken. Several genes were over-expressed in 12q13, including cytokeratin 6B (KRT6B) ( approximately 10-fold), epidermal growth factor receptor ERBB3 (approximately 4.7-fold), and glioma-associated oncogene homologue 1 (GLI1) (approximately 5- to 12-fold). One amplicon (approximately 0.7 Mega base pairs [Mbp]), covering several genes involved in the regulation of cell growth, was found in 12q13.2. Deletions were found in 3q13.1, 5p14.3, and 7q31.3, including the cell-adhesion-related gene cadherin 18 (CDH18) and leukocyte cell adhesion molecule (ALCAM, MEMD). Over-expressed and amplified genes in 12q13, also reported in several other tumors and cell lines, may contribute to the persistent growth characteristics of KCOT.
Full-text · Article · Jul 2007 · Journal of Dental Research