The Expression And Biological Significance Of PDCD4 And MMP-14 In Cervical Squamous Cell Carcinoma

PDCD4 is a tumor suppressor gene, which makes the Cyt C release into the cytoplasm from the mitochondrial membrane space, there by leading to apoptosis through mitochondrial pathway, triggering caspase cascade reaction to induce apoptosis in cancer cells. MA3 are two importantα-helix structure areas at the amino side of PDCD4. PDCD4 bind eukaryotic translation initiation factor eIF4A through MA3. Thus effectively inhibit protein synthesis, and promote apoptosis. PDCD4 and eIF4G also has significant amino acid homology. MA3 in PDCD4 contains two conserved regions also seen in the eukaryotic translation initiation factor eIF4G I and eIF4GⅡ. MA3 relate to protein interactions, and could allow eIF4G and eIF4A interaction. EIF4A is an ATP-dependent RNA helicase. It can unwind mRNA and fix ribosomes at the start codon AUG in the 3'end. PDCD4 protein can directly interact with eIF4A, restrain the function of protein translation.MMP-14 is membrane-type matrix metalloproteinase, located in the membrane. MMP-14 can degradeⅠ,Ⅱ,Ⅳcollagen and FN, including participate in degradation of basement membrane and other extracellular matrix. Extracellular matrix and basement membrane is a barrier to tumor growth and spread. Tumor cells infiltrating and metastasis depend on MMPs degrade extracellular matrix. In this study, we use immunohistochemistry and PT-PCR to detect PDCD4 and MMP-14 expression in normal cervix and cervical squamous cell carcinoma. Investigate the relationship between the pathological grade of cervical squamous carcinoma and PDCD4 and MMP-14 expression. Investigate the effect of PDCD4 and MMP-14 in tumorigenesis,development and metastasis of cervical cancer.Results:(1) Positive particle of PDCD4 could ce seen at nucleus and cytoplasm in normal cervical tissue with immunohistostaining. In cervical squamous carcinoma, positive particle of PDCD4 could be found at cytoplasm with the same staining.But the positive particle decreased as the degree of differentiation. In well-differentiated cervical squamous carcinoma, positive particle positive expression that could be found at nucleus and cytoplasm; weakly positive particle was found in moderately differentiated cervical squamous carcinoma; the expression of PDCD4 is weakly positive or no positive in poorly differentiated cervical squamous carcinoma. The expression of PDCD4 was found no significant differences in normal cervix and well-differentiated cervical squamous carcinoma.With the increase of pathological grades, the expression of PDCD4 down-regulation obviously. The significant differences of the PDCD4 mRNA was found in normal cervix and poorly differentiated cervical squamous carcinoma.The expression of PDCD4 mRNA down-regulated or absence following the raise of pathological gardes.(2)No positive particles of MMP-14 protein were found in normal cervix. The positive particles mainly could be seen at cytoplasm in cervical squamous carcinoma. Positive particles were found in cytoplasm and its stain intensity is weak in well-differentiated cervical squamous carcinoma. The stain intensity of moderately-differentiated cervical squamous carcinoma is moderate and the positive particles were also found in cytoplasm. The strong positive particles were found in poorly-differentiated cervical squamous carcinoma and some of the inflammatory cells adjacent tumor tissue express positive particles.The significant differences were found in normal cervix and cervical squamous carcinoma,and the expression of MMP-14 become strong following up of pathological grades. According to RT-PCR results showed that the expression of MMP-14 mRNA were found no significance difference between normal cervix with well-differentiated cervical carcinoma,but the significance differences were found in normal cervix, moderated-differentiated and poorly-differentiated cervical carcinoma.Conclusion:The action of PDCD4 and MMP-14 was not same in cervical squamous carcinoma, but both factors play an important role in the development of cervical squamous carcinoma.The expression of PDCD4 gene and encodes protein down-regulated obviously or absence in cervical squamous carcinoma. It was shown that PDCD4 gene inactivation involve in invasion and metastasis of cervical squamous carcinoma and the expression of PDCD4 also related to differentiation of cervical squamous carcinoma. The expression of MMP-14 is up-regulated in cervical squamous carcinoma; demonstrate the expression of MMP-14 maybe enhances the infiltration and metastasis ability of tumor. Maybe PDCD4 and MMP-14 play an important role in invasion and metastasis of cervical squamous carcinoma. Both PDCD4 promoter and MMP-14 selective inhibitor could be use for prevention and therapy to cervical carcinoma.