| Prostate cancer (PCa) is a malignant tumor in elderly man. The mechanism about PCa’s germination and development has been attached important to for its high morbidity and cacoethic therapy effect and prognosis. This article is composed of three parts.The first part is about the expression of PTEN gene in PCa and the expression’s relativity between PTEN gene and androgen receptor (AR). PTEN gene is another anti-oncogene besides p53. It has double activity about lipide phosphatase and protein phosphatase. The expression deficiency of PTEN gene is relative with many malignant tumors, including PCa. It has important value for the study on the mechanism about PCa’s germination and development to detect the expression of PTEN gene in PCa. Meanwhile, AR plays an important role in prostate growth, engender and its normal function. AR plays an important role in BPH and PCa’s germination and development, too.41 cases PCa’s lesions tissue diagnosed by pathology were obtained through puncture guiding by ultrasonic, and contrasted by 30 cases BPH’s tissue diagnosed by pathology. The expression of PTEN and AR were detected in puncture tissue by RT-PCR, and tested by Western blot. The relativity was analyzed between the expression of PTEN and AR, clinical stage, Gleason score in PCa. The relativity between the expression of PTEN and the expression of AR was analyzed too.The relativity between the expression of PTEN and AR and disease progress in PCa was discussed, including the relativity between PTEN’s expression and AR’s expression. Compare to BPH, the expression of PTENmRNA and PTEN was significantly lower in PCa (P<0.01) in each clinical stage. The expression of PTENmRNA and PTEN was negatively related to clinical stage(r=-0.997 and -0.710, P<0.01). The expression of PTEN was significantly lower in PCain high and middle differentiation group(Gleason score<7) and low differentiation group(Gleason score>8)(P<0.01). The expression of PTENmRNA and PTEN was negatively related to Gleason score (r=-0.672 and -0.409, P<0.01).The expression of ARmRNA and AR in early PCa was higher than BPH (P<0.05), but it appears significant decreased in the advanced clinical stage (P<0.01). The expression of ARmRNA and AR was negatively related to clinical stage (r=-0.785 and -0.860, P<0.01). The expression of ARmRNA and AR was significantly higher in PCa (P<0.01) in high and middle differentiation group(Gleason score≤7), and significantly lower in low differentiation group(Gleason score≥8) (P<0.01). The expression of ARmRNA and AR was negatively related to Gleason score (r=-0.560 and -0.709, P<0.01). In the advanced clinical stage and Gleason score,the expression of PTENmRNA/PTEN and ARmRNA/AR was lower, the expression of PTENmRNA correlated with ARmRNA expression (r=0.641, P<0.01), and the expression of PTEN correlated with AR expression (r=0.557, P<0.01)The second part is an experiment study on the negative role of PTEN gene in Raf-1 phosphorylation in prostate cancer cell line PC3. The anti-oncogene PTEN and AR played a role in PCa through many cell signaling pathway, especially in AIPC, such as PI3K/AKT, MAPK/ERK, et al. PTEN and AR play an important role trough promoting or inhabiting phosphorylation of the signaling protein in the pathway. In the pathway, each signaling protein accomplishes their control effect through interreaction in their pathway or among the different pathway. It should contribute to reveal the molecular biology mechanism of AIPC to observe the PTEN’s function in signaling pathway. It has been clear that PTEN’s action on the AKT in PI3K/AKT signaling pathway. It will be focal point in this part whether there was any PTEN’s effect point in MAPK/ERK pathway besides Ras, MEK and ERK. According to the characteristic of MAPK/ERK pathway, the signaling protein Rafl was selected as study target. Prostate cancer cell line PC3, disposed by Ras’inhibitor FTS (150μmol/L) and AKT’s inhibitor MK2206 2HC1 (3μmol/L), was observed its change of phosphorylation in the different PTEN’s expression in order to reveal the effect of Rafl phosphorylation in different PTEN’s expression. It’s showed in PC3 cells, that the Rafl phosphorylation level decreased by 61.1%(P<0.01) when PTEN was overexpressed, and increased by 75.1%(P<0.01)when PTEN gene was silenced. It has been pointed out in our study that PTEN was a negative regulator of the Rafl phosphorylation in PC3, and Rafl is another new effect point besides Ras, MEK and ERK in MAPK/ERK signaling pathway. It has been contributed to reveal the mechanism of PCa’s germination, and treatment on the target as PTEN, Rafl and MEK in the signaling pathway.The third part is an experiment study on the role of PTEN gene in prostate cancer cell line PC3’s apoptosis through its negative role in Rafl phosphorylation. Apoptosis is one of important physiology functions in cells. It is also a course of cells’active death that controlled by gene. Apoptosis plays an important role in maintaining the balance of cell’s hyperplasia and survival; meanwhile, it will influence tumors’ germination and growth. PTEN gene plays a negative role in Rafl phosphorylation in prostate cancer cell line PC3, and change the activity of MEK 1/2 and ERK 1/2. MAPK/ERK signaling pathway can act on apoptosis through interrelated way. On the basis of PTEN gene’s negative function in Rafl phosphorylation, prostate cancer cell line PC3, disposed by Ras’inhibitor FTS(150μmol/L)and AKT’s inhibitor MK2206 2HCl(3μmol/L), was observed its change of apoptosis. It’s showed in PC3 cells, when PTEN gene was overexpression, Rafl phosphorylation was lower, the change of cellular morphology occurred, the survival rate on CCK-8 was (49.60±0.52)% and reduced to control (P<0.01), the apoptosis rate was (25.07±0.25)% and increased to control (P<0.01). And the meanwhile, caspase-8, caspase-9, caspase-12, caspase-3 and Bax were overexpression, Bcl-2 was low expression(P<0.01). When PTEN gene was silenced, Rafl phosphorylation was higher, the survival rate on CCK-8 was (113.45±1.16)% and increased to control (P<0.01), the apoptosis rate was (0.133±0.058)% and reduced to control (P<0.01), the expression of caspase-8, caspase-9, caspase-12, caspase-3 and Bax were lower, Bcl-2 was overexpression(P <0.01). It has been pointed out in our study that apoptosis can be influenced in prostate cancer cell line PC3 by PTEN gene through Raf-1 phosphorylation and activity of MAPK/ERK signaling pathway. It has been contributed to the basis of new target of PCa and AIPC’s diagnosis and treatment, according to the signaling protein in MAPK/ERK signaling pathway and the protein in apoptosis, e.g., caspase and Bcl-2/Bax. |
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