Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer

2011 ◽  
Vol 51 (11) ◽  
pp. 916-922 ◽  
Author(s):  
Michael Sand ◽  
Marina Skrygan ◽  
Dimitrios Georgas ◽  
Christoph Arenz ◽  
Thilo Gambichler ◽  
...  
2011 ◽  
Vol 34 (6) ◽  
pp. 339-353 ◽  
Author(s):  
Julia Knaup ◽  
Christina Gruber ◽  
Barbara Krammer ◽  
Verena Ziegler ◽  
Johann Bauer ◽  
...  

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary skin disorder characterized by mechanical fragility of the skin, resulting in blistering and chronic wounds. The causative mutations lie in the COL7A1 gene. Patients suffering from RDEB have a high risk to develop aggressive, rapidly metastasizing squamous cell carcinomas (SCCs). Cutaneous RDEB SCCs develop preferentially in long-term skin wounds or cutaneous scars. Albeit being well differentiated, they show a more aggressive behavior than UV-induced SCCs. These findings suggest other contributing factors in SCC tumorigenesis in RDEB.Objective: To analyze factors contributing to RDEB tumorigenesis, we conducted a comprehensive gene expression study comparing a non-malignant RDEB (RDEB-CL) to a RDEB SCC cell line (SCCRDEB4) to achieve an overview on the changes of the gene expression levels in RDEB related skin cancer.Methods: We applied cDNA arrays comprising 9738 human expressed sequence tags (EST) with various functions. Selected results were verified by Real-time RT PCR.Results: Large-scale gene expression analysis revealed changes in the expression level of transforming growth factor β1 (TGFβ1) and several genes under the control of TGFβ for RDEB and SCCRDEB4 cell lines. Even untransformed RDEB keratinocytes show elevated levels of TGFβ1.Conclusion: Our findings demonstrate a prominent role of TGFβ-signaling in RDEB-related skin cancer. Once activated, TGFβ signaling either in response to wounding or in order to influence type VII collagen expression levels could facilitate cancer development and progression. Moreover, TGFβ signaling might also represent a potentially useful therapeutic target in this disease.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Masayuki Matsui ◽  
Liande Li ◽  
Bethany A. Janowski ◽  
David R. Corey

Author(s):  
Joshua Ravicz ◽  
Christopher Szeto ◽  
Sandeep Reddy ◽  
Sant Chawla ◽  
Michael Morse ◽  
...  

Background: Metastatic cancer is associated with an invariably fatal outcome. However, DeltaRex-G, a tumor- targeted retrovector encoding a CCNG1 inhibitor gene, has induced long term (>10 years) survival of patients with chemo-resistant metastatic pancreatic adenocarcinoma, MPNST, osteosarcoma, B-cell lymphoma, and breast carcinoma. Objective: To evaluate the level of CCNG1 expression in tumors as a potential biomarker for CCNG1 inhibitor therapy. Methods: CCNG1 RNA expression levels were measured in tumors (TCGA, N=9161), adjacent “tissues” (TCGA, N=678) and GTEx normal tissues (N=7187) across 22 organ sites. Differential expression of CCNG1 and Ki-67 in primary (N= 9161) vs metastatic (N= 393) tumors were also compared and particularly in primary (N=103) vs. metastatic (N=367) skin cancer (i.e., melanoma). Results: Enhanced CCNG1 RNA and protein expression were noted in tumors compared to normal analogous counterparts, and CCNG1 expression correlated significantly with that of Ki-67. Further, CCNG1 expression tended to be higher than that of Ki-67 in metastatic vs primary tumors, particularly in skin cancer (melanoma). Conclusions: Taken together, these data indicate that (1) CCNG1 expression is frequently enhanced in tumors when compared to their normal analogous counterparts, (2) CCNG1 and Ki-67 expressions are higher in metastatic vs primary tumors, (3) CCNG1 expression is significantly correlated with that of Ki-67, and (4) CCNG1 may be a stronger marker of metastasis than Ki-67. Phase 2 studies are planned to identify patients who are likely to respond favorably to CCNG1 inhibitor therapy by correlating treatment outcome parameters with CCNG1 expression levels in various cancer types.


2013 ◽  
Vol 14 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Bora Kim ◽  
Jae-ho Lee ◽  
Jong Wook Park ◽  
Taeg Kyu Kwon ◽  
Seong Kyu Baek ◽  
...  

2016 ◽  
Vol 31 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Elham Erfani ◽  
Raheleh Roudi ◽  
Azadeh Rakhshan ◽  
Mehrdad Nasrollahzadeh Sabet ◽  
Ahmad Shariftabrizi ◽  
...  

Introduction Skin cancers, particularly melanoma, are initiated and maintained by a subpopulation of tumor cells expressing stemness markers that are called cancer stem cells (CSCs). This study aimed to evaluate the expression levels and clinicopathological significance of the putative CSC markers CD44 and ALDH1A1 in patients with skin cancer. Methods The expression levels of CD44 and ALDH1A1 were investigated in 107 skin cancer specimens including 58 (54%) basal cell carcinomas (BCC), 37 (35%) squamous cell carcinomas (SCC), and 12 (11%) melanomas using the tissue microarray (TMA) technique. The correlation of the expression levels of these markers and clinicopathological parameters was then analyzed. Results The expression levels of CD44 and ALDH1A1 were significantly higher in melanoma patients than patients with SCC or BCC (p<0.001 and p = 0.002, respectively). A higher level of CD44 expression was more often found in melanoma tumor cells with a higher rate of recurrence (p = 0.029) and in SCC cases with ulceration (p = 0.01), while there was no significant correlation between ALDH1A1 expression and other clinicopathological parameters. Similarly, coexpression of CD44 and ALDH1A1 (CD44high/ALDH1A1high) was significantly observed in melanoma samples (p<0.001). Conclusions These findings suggest that a CD44high/ALDH1A1high phenotype in melanoma and a CD44high phenotype in SCC can be considered candidates for targeted therapy of skin cancers aiming at CSCs.


2010 ◽  
Vol 28 (6) ◽  
pp. 649-653 ◽  
Author(s):  
Michael Sand ◽  
Thilo Gambichler ◽  
Marina Skrygan ◽  
Daniel Sand ◽  
Nina Scola ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1151 ◽  
Author(s):  
Montserrat Fernández-Guarino ◽  
José Javier Zamorano León ◽  
Antonio José López Farré ◽  
Maria Luisa González Morales ◽  
Ana Isabel Sánchez Adrada ◽  
...  

Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non-melanoma skin cancer and is the second leading cause of death by skin cancer in Caucasian populations. However, at present it is difficult to predict patients with poor SCC prognosis. Objective: To identify proteins with expression levels that could predict SCC infiltration in SCC arising from actinic keratosis (SCC-AK). Methods: A total of 20 biopsies from 20 different patients were studied; 10 were SCC-AK samples and 10 were taken from normal skin. Early infiltrated SCC-AK samples were selected based on histological examination, and to determine the expression of proteins, fresh skin samples were processed by two-dimensional electrophoresis. Results: The expression levels of three proteins, namely alpha hemoglobin and heat shock proteins 27 and 70 (Hsp27 and Hsp70, respectively) were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immunohistological examination suggested that increased expression of Hsp70 proteins seemed to mainly occur in the cytoplasm of keratinocytes. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western blot experiments. Conclusion: Cytoplasmic expression of Hsp70 could be a potential biomarker of early infiltration of SCC arising from AK.


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