involucrin and Carcinogenesis

Topics: Animals; Calmodulin-Binding Proteins; Carcinogenesis; Cell Cycle; Cell Differentiation; Cells, Cultured; CHO Cells; Codon Usage; Cricetulus; Female; HEK293 Cells; Human papillomavirus 16; Humans; Keratinocytes; Mice; Mice, Inbred C57BL; Papillomavirus E7 Proteins; Phosphorylation; Protein Precursors; Repressor Proteins; Spectrin

HOXA13 overexpression has been detected in human ESCC tissue and high HOXA13 protein expression is correlated with a shorter median survival time in ESCC patients. Although aberrant expression of HOXA13 in ESCC has thus been established, little is known regarding the functional consequences thereof. The present study aimed to examine to what extent aberrant HOXA13 might drive carcinogenesis in esophageal keratinocytes. To this end, we overexpressed HOXA13 in a non-transformed human esophageal cell line EPC2-hTERT, performed gene expression profiling to identify key processes and functions, and performed functional experiments. We found that HOXA13 expression confers oncogenic hallmarks to esophageal keratinocytes. It provides proliferation advantage to keratinocytes, reduces sensitivity to chemical agents, regulates MHC class I expression and differentiation status and promotes cellular migration. Our data indicate a crucial role of HOXA13 at early stages of esophageal carcinogenesis.

Topics: Carcinogenesis; Carcinoma, Squamous Cell; Cell Adhesion; Cell Differentiation; Cell Line, Transformed; Cell Movement; Esophageal Neoplasms; Esophagus; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Histocompatibility Antigens Class I; Homeodomain Proteins; Humans; Keratin-19; Keratinocytes; Neoplasm Proteins; Phosphoproteins; Protein Precursors; Signal Transduction; Spheroids, Cellular; Survival Analysis

To assess the level of maturation and proliferation of epithelial cells and the correlation with immunocytochemical expression of adhesion (E-cadherin) and cell differentiation (involucrin) markers.. Cytopathological samples were obtained from four groups of patients: control (CG, n=30); alcohol/tobacco (ATG, n=31), leucoplakia (LG, n=31), and squamous cell carcinoma (SCCG, n=22). Cytopathological smears were collected from all groups for AgNOR, Papanicolaou and immunocytochemical staining.. There was an increase in anucleated cells in ATG compared to CG and in LG compared to lesion-free groups (P<.05). In addition, there was a higher rate of intermediate cells in lesion-free groups than in LG (P=.001). When these findings were correlated with positive E-cadherin expression, there was a smaller number of anucleated and intermediate cells (P<.05). The proliferation rate was higher in the SCCG than in the CG (P<.05) and in the ATG compared to LG (P<.05). Moreover, cell proliferation increased in the presence of positive E-cadherin expression in the ATG and LG. No statistically significant results were obtained for involucrin analysis.. Cytopathology combined with quantitative techniques such as Papanicolaou, AgNOR, and immunocytochemical expression of E-cadherin detects changes associated with oral carcinogenesis. The innovative approach used in this study allows assessing the expression of cell adhesion (E-cadherin) and differentiation (involucrin) markers by means of oral mucosal cytopathology. The E-cadherin imunocytochemical expression indicated changes associated with the oral carcinogenesis process. An increase in cell proliferation rate in oral squamous cell carcinoma group was associated with the lower immunoexpression of E-cadherin. Cytopathology combined with quantitative techniques and immunocytochemical expression of E-cadherin may detect early alterations associated with oral carcinogenesis.

Topics: Antigens, CD; Cadherins; Carcinogenesis; Carcinogens; Cell Proliferation; Female; Humans; Leukoplakia, Oral; Male; Mouth Neoplasms; Precancerous Conditions; Protein Precursors; Squamous Cell Carcinoma of Head and Neck; Tumor Cells, Cultured

Hematopoietic pre-B-cell leukemia transcription factor-interacting protein (HPIP) is a corepressor of pre-B-cell leukemia homeobox (PBX) 1 and is known to play a role in hematopoiesis. Recently, HPIP was demonstrated to promote breast cancer cell proliferation and hepatocellular carcinoma growth. Moreover, it has been revealed that homeobox and PBX proteins, the expression of which is regulated by HPIP, play key roles in cancer of various organs, including oral squamous cell carcinoma (OSCC). Nevertheless, there has not been any study regarding the role of HPIP in OSCC. This study investigated the expression of HPIP in normal oral mucosa, epithelial precursor lesion (OEPL), and OSCC, and the functional roles of HPIP in OSCC cells and normal keratinocytes.. Immunohistochemical analysis of HPIP, Ki-67, and involucrin was performed in OSCC specimens, and the change in involucrin expression following RNA interference treatment against HPIP was examined by quantitative RT-PCR and Western blot analysis in SCC9 and NHEK cells undergoing extracellular calcium-induced differentiation. Matrigel transwell and cell proliferation assays for both cell lines transfected with HPIP siRNA were also conducted.. HPIP expression increased in OEPL and OSCC specimens. In vitro analysis revealed that HPIP suppressed differentiation and proliferation of SCC9 cells and transwell migration of NHEK cells, while HPIP promoted invasion of SCC9 and proliferation of NHEK cells. However, HPIP has no significant effect on NHEK cell differentiation.. HPIP may play a critical role in oral carcinogenesis and is thus a potential target for anticancer therapy, with particular emphasis on its involvement in differentiation and migration/metastasis.

Topics: Adult; Aged; Calcium; Carcinogenesis; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Co-Repressor Proteins; Female; Gene Silencing; Humans; Keratinocytes; Ki-67 Antigen; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions; Protein Precursors; RNA, Small Interfering; Transcription Factors