| Background: Breast cancer is the second leading cause of cancer death in woman, metastasis is a multistep process responsible for breast cancer deaths. The 5-year survival rate for breast cancer patients with distant metastases the survival rate is only 23%. Therefore, it is important to have a better understanding of the molecular mechanisms underlying breast cancer metastasis for the design of novel therapeutics. Lysyl oxidase(LOX)is the key enzyme that controls collagen and elastin maturation and stabilizes extracellular matrix. Several reports have suggested a clear association between organ fibrosis and increased LOX activity. Recent reports have demonstrated novel roles for LOX, including the ability to regulate gene transcription, motility/migration, and cell adhesion. LOX expression that have been observed in various cancerous tissues and neoplastic cell lines. Both down and up regulation of LOX in tumor tissues and cancer cell lines have been described, suggesting a dual role for LOX as a tumor suppressor and a metastasis promoter gene. The literature demonstrates the increasingly important role(s) that LOX may play in regulating tumor progression.Objective:To study the expression of LOX in human breast cancer and explore the relationship between LOX expression and clinical pathological features(patient's age, tumor size, limph node metastasis, clinical stage, ER, PR and HER-2)in human breast cancer, and the expression of HIF-1, PCNA, Ki-67, MMP-2 and MMP-9.Method:1. The expression of LOXmRNA and HIF-1αmRNA in 56 cases of human breast cancer tissues, normal breast tissues and 20 cases of breast benign lesion tissues was detected by reverse transcriptase polymerase chainreaction (RT-PCR).2. The expression of LOX, HIF-1α, PCNA, Ki-67, MMP-2 and MMP-9 protein in 56 cases of human breast cancer tissues, normal breast tissues and 20 cases of breast benign lesion tissues were detected by S-P immunohistochemistry.Results:1. The expression rate of LOXmRNA in breast cancer,normal breast tissues and breast benign lesion tissue were 57.14% ,32.14% and 25.00% , statistical difference was found among them (P=0.007); statistical difference was found among breast carcinoma group, normal breast tissues group and benign lesion group.2. The expression of LOXmRNA were associated with clinical stage (P=0.001) and lymph node metastasis (P=0.013), but had no correlation with age and tumor size (P>0.05).3. The expression rate of LOX protein in breast cancer, normal breast tissues and breast benign lesion tissue were 48.21%, 26.78% and 20.00%, statistical difference was found among them (P=0.019); statistical difference was found among breast carcinoma group, normal breast tissues group and benign lesion group.4. The expression of LOX protein were associated with clinical stage (P=0.005), lymph node metastasis (P=0.042) and tumor size (P=0.021), but had no correlation with age (P>0.05). The LOX protein shew significant positive correlation with the Ki67(r=0.367,P=0.005), PCNA(r=0.330,P=0.013)and HIF-1α(r=0.368,P=0.005)protein expression in breast cancer, but had no correlation with MMP-2, MMP-9, ER, PR and HER-2 (P>0.05).Conclusion:1. LOX protein and LOXmRNA expression is increased in breast cancer tumor tissues compared with normal tissues and breast benign lesion tissue, LOX is relevant with the occurrence of breast cancer.2. The breast cancer cells proliferation capacity is increase, degree of malignancy is higher and facilitates metastasis occurred which LOX is expressed.3. The mechanisms of LOX promote breast cancer invasion and metastasis is different from MMP-2 and MMP-9, it is unrelated with the changes of ECM.4. LOX and HIF-1αhave a synergistic effect in breast cancer invasion and metastasis.5. There are no difference between The sensitivity of LOX protein detected by S-P immunohistochemistry and LOXmRNA detected by RT-PCR. |
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