The Expression Of ARHI In Oral Premalignant Lesions And Squamous Cell Carcinomas

Background: With the growing maturity of molecular biology, cancer gene research into the current hot spots. Tumor development is due to tumor-related gene mutation, associated with proliferation or apoptosis, including tumor suppressor gene inactivation or deletion in the tumor and has an important role in the development process. YU, etc. Since 1999, with the difference PcR from human ovarian and breast epithelial cells and cancer cells to the tumor suppressor gene was cloned ARHI, the gene as a new tumor suppressor gene, has aroused increasing concern.We recently identified Ras homolog member I (ARHI), a novel maternally imprinted tumor suppressor gene that encodes a 26 kDa GTP-binding protein with high homology to Ras and Rap. Unlike other Ras family members, ARHI exhibits several unusual structural and functional properties. ARHI contains a unique 34 amino-acid extension at the N-terminus, and differs from Ras in residues critical for GTPase activity and in its putative effector domain. Like Ras, ARHI can bind to GTP with high affinity but has low intrinsic GTPase activity. In addition, while Ras is an oncogene, ARHI functions as an inhibitor for cell growth. 32Phosphorus labeling showed that ARHI is maintained in a constitutively activated GTP-bound state in resting cells, possibly because of impaired GTPase activity. ARHI is associated at the cell membrane through its prenylation at the C-terminal cysteine residue. Mutation of the conserved CAAX box at the C-terminus led to a loss of its membrane association and a decreased ability to inhibit cell growth. Conversion of Ser51 to Asn decreased GTP binding and reduced ARHI's biological activity. Mutation of Ala⁴⁶ to Val increased the ability of ARHI to inhibit cell growth, associated with a further decrease of its intrinsic GTPase activity. Moreover, conversion of residues in ARHI that are conserved in the Ras family for GTPase activity partially restored the GTPase activity in ARHI. Most strikingly, deletion of ARHI's unique N-terminal extension nearly abolished its inhibitory effect on cell growth, suggesting its importance in ARHI's inhibitory function. Thus, ARHI is a unique Ras family member that retains basic small GTPase function, but exhibits many unusual features. In contrast to most other Ras family members, ARHI has a long N-terminal extension, modest GTPase activity, and constitutive GTP binding in resting cells. Furthermore, unlike the Ras oncogene, ARHI inhibits cell growth, and loss of its expression in cells may contribute to the development of breast and ovarian cancers.The occurrence and development of cancer is recognized as a multigene complex in the multi-step process. In this complex process, the tumor suppressor gene inactivation or loss is a common and important cause of tumor molecular biology. It may be an important protection against tumor mechanism. Oral squamous cell carcinoma is one of the most common oral cancer, the incidence rate, survival rate, serious harm to human health. The development of oral squamous cell carcinoma involving a variety of oncogenes and tumor suppressor gene structure and function, this experiment of ARHI in oral precancerous lesions and oral squamous cell carcinoma cases.Objective:To detect ARHI in normal oral mucosa, lichen planus and oral squamous cell carcinoma to explore their development in oral squamous cell carcinoma and its future in the role of the relevant sections of the diagnosis in the oral cavity to provide a better theoretical basis.Methods:From April 2010 to January 2011 during the VIP General Hospital, Jilin University, Department of Oral biopsy or surgical specimens. Including 10 cases of normal oral mucosa, lichen planus in 18 cases, 30 cases of oral squamous cell carcinoma. Immunohistochemistry were used (SP) and RT-PCR technique to detect the expression. Results:1 ARHI in 10 cases of normal oral mucosa of all positive (100%), 16 cases of lichen planus tissue, 14 cases were positive (87.5%), the two groups was no significant difference (P> 0.05); 30 cases of squamous cell carcinoma, 18 cases were positive (60%), normal group, lichen planus and squamous cell carcinoma had significant differences (P <0.05).2 ARHI in different tissues of the average optical density in normal oral mucosa and lichen planus was no significant difference (P> 0.05), and well differentiated, moderately differentiated, poorly differentiated squamous cell carcinoma were significantly different than (P <0.01) ; lichen planus and well-differentiated, moderately differentiated squamous cell carcinoma a significant difference (P <0.05), compared with poorly differentiated squamous cell carcinoma were significantly different (P <0.01); in well differentiated squamous cell carcinoma and squamous cell carcinoma was not significantly differences (P> 0.05), compared with poorly differentiated squamous cell carcinoma were significantly different (P <0.01); differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma in a significant difference (P <0.05).3 ARHI in normal oral mucosa, lichen planus and oral squamous cell carcinoma have different levels of expression. Paired variance test, ARHI in normal oral mucosa tissues were significantly higher than other tissues (P <0.05), ARHImRNA in normal oral mucosa and lichen planus showed no significant difference (P> 0.05), while in normal oral mucosa and squamous cell carcinoma with significant difference (P <0.05).Conclusion:1 shows the results of immunohistochemistry, tumor suppressor gene ARHI in normal oral mucosa, lichen planus, oral squamous cell decreased gradually.2 tumor suppressor gene ARHI in normal oral mucosa and lichen planus expression difference was not significant, but with oral squamous cell differentiation between the different organizations are significantly different3 RT-PCR results showed that, ARHI expression in oral squamous cell carcinoma compared with normal oral mucosa and lichen planus was significantly reduced.4 ARHI in normal oral mucosa, lichen planus tissue the expression of oral squamous cell carcinoma of the lower levels or absent, indicating that apoptosis of ARHI gene mutation or deletion may be associated with oral squamous cell carcinoma and the development of an important relationship.