Expression Of Pak1 Gene In Breast Carcinoma And Its Clinical Significance

Background and ObjectBreast cancer is one of the most common malignancy of women, mainly between the ages of 40-60.With the improvement of people's standard of living and changes of lifestyle and the structure of diet, the incidence of breast cancer has increased year by year, and the age of onset has inclined to get younger. The occurrence of breast cancer is a multi-factor, multi-mutation accumulation process. So far the pathogenesis remains unknown. Researches with regard to the occurrence, development and metastasis-associated protein over-expression and activation of breast cancer have been hot in this field.Pakl (p21-activated kinase-1, p21 activated kinase 1) gene is located in human chromosome 11q13.5-q14 area, the study found that the gene abnormalities and breast cancer and leukemia and other malignant tumors were closely related to the occurrence and development (1-2) of the disease. For breast tumor cells, survival, mitosis, cytoskeleton regeneration reorganization, cell migration, as well as progress in hormone-dependent, it plays an important role. In this study, real-time fluorescent quantitative RT-PCR and immunohistochemistry were used to detect pakl gene mRNA abundance and protein content in breast cancer tissues. Studies of patients with clinical and pathological data will provide a better understanding of their tumor occurrence and development of the molecular mechanisms and clinical pathological significance.MethodsThe mRNA expression of pakl gene were detected in 35 cases of breast carcinoma and 10 cases of benign mammary lesions and 15cases of normal lobular tissue by fluorescent real-timg RT-PCR, which take SYBR Green I as fluorescent dye and house-keeping gene as intra-control. Ststistial analysis was carried out to analyze the correlation between Pakl gene expression and clinical significance in these breast cancer patients on transcriptional level. The protein expression of Pakl were detected in 35 cases of breast carcinoma and 15cases of normal lobular tissue by immunohistochemcal study. Stastistial analysis was carried out to analyze the correlation between Pakl gene expression and clinical significance in these breast cancer patients on protein level.ResultsThe relative expression level of PAK1 mRNA and protein are:(1)The relative expression of Pakl mRNA were 0.94±0.06 in 15cases of normal lobular tissue; the relative expression of Pakl mRNA were 2.66±0.10 in 10 cases of benign mammary lesions, in contrast to 35 cases of breast carcinoma; the relative expression of Pakl mRNA were 4.76±0.11, which was significantly higher than the other groups(P<0.003). (2)The relative expression of Pakl mRNA were 4.59±0.57 in 14 speciments of ER-negative, in contrast to 21 speciments of ER-positive; the relative expression of Pakl mRNA were 5.04±0.69,which was significantly higher than the other groups(P=0.038). (3) Immunohistochemical staining results:Pakl gene was overexpression in 8 speciments of 14 cases of ER-negative(57.14%), in contrast to 19 speciments of 21 cases of ER-positive(90.48%), which was significantly higher than the other groups (P＜0.05); Pakl gene was overexpression in 7 speciments of 13 cases of PR-negative (53.85%), in contrast to 20 speciments of 22cases of PR-positive(86.96%), which was significantly higher than the other group(P<0.05). (4)Neither mRNA nor protein expression of Pakl gene correlated with the age of patients, size of tumor, Lymph node metastasis and the level of CerbB-2(P>0.05).ConclusionsAs an oncogene,Pakl participated in the carcinogenesis,development and prognosis of breast carcinoma. Pakl over expression is a common phenomenon in breast cancer, and may be related to the level of ER and PR of breast carcinoma;but was not associated with the age of patients,size of tumor, Lymph node metastasis, the level of CerbB-2. Pakl in the tumor cell plays an important role in immune escape, exercise, angiogenesis and gene regulation. Therefore,Pakl is a key point where signal conduction pathway with progression of breast carcinoma.To enforce the intervention on the signal conduction with Pakl will certainly to induce the apotosis in breast cancer cell,inhibiting proliferation,and inhibiting tumor angiogenensis.It is valuable for the early diagnosis and prognosis judgement in breast carcinoma through detected the level of Pakl quantity.