| Colorectal cancer is a common cause of cancer death in China. With theimprovement of living condition and increased tendency of western lifestyle, the morbidity has increased over the decade. The development and progression of colorectal cancer is a complex multistep process involving numerous molecular events, such as activation of oncogenes and inactivation of suppressor genes. Though many genes have been reported to be closely related with the carcinogenesis of colon and rectum, they are not enough to explain the transformation and still a lot of other genes, known or unknown, are waiting to be disclosed.B2 is a cDNA fragment which is separated from colonic adenocarcinoma -normal mucosa cDNA substraction library by SSH. It shares 97% identity with the cDNA sequence of IGFBP-rP1, and is found to be expressed higher in colonic adenocarcinoma than in adenoma and in paired normal tissue by Northern Blot.The IGF axis is made up of a series of members including IGF-I.II, IGF R-l.ll. IGFBPs and IGFBP proteases. IGFs have numerous functions: they are potent mitogens, act as anti-apoptotic survival factors, have a role in glucose metabolism and promote cell migration. These effects are predominantly mediated via the IGF7Rs. however the circulating levels of IGFs are subject to complex physiological regulations. The vast majority of circulating IGFs are bound to IGFBPs. IGFBPs modulate the bioactivity of IGFs mainly in the following three ways: 1. elongate the half-life of IGFs. 2. inhibit the binding of IGFs to IGF Rs. 3. carry them to tissues. IGFBP-rP1 is a member of IGF signal transduction system, which shares high similarity in the N-terminal domain with IGFBP 1-6. It can be bound with IGFs and insulin with a high affinity, and thus adjusts the bioavailibility of IGFs and insulin. The function of IGFBP-rP1 is complex and still largely unknown at present. It is demonstrated that IGFBP-rP1 is widely distributed in normal tissues, and highly accumulated in blood vessels within tumor tissues, but not in those within normal tissues. This protein also stimulates adhesion of vascular endothelial cells to plastic substrates and promotes the spreading of rat liver cells through plastic substrates. These facts suggest that IGFBP-rP1 might play an important role in the angiogenesis or infiltration or metastasis of tumor cells. However, it is also reported that down-regulated expression of IGFBP-rP1 is a common phenomenon in tumors from prostate, breast, liver and in meningiomas. Overexpression of IGFBP-rP1 results in the decreased colony formation in soft agar and increased propensity to undergo apoptosis. The expression of IGFBP-rP1 is significantly higher in senesent mammary epithelial cells and prostate cells than that in quiescent ones. These data suggest that IGFBP-rP1 might be a tumor suppressor gene. But inconsistant findings also exist. The overexpression of IGFBP-rP1 in myoblast can inhibit differentiation, and up-regulated expression of IGFBP-rP1 is observed in prostate adenocarcinomas, colon cancers and in cerebrospinal fluid of children with acute lymphoblastic leukemia. In conclusion, IGFBP-rP1 appears to be involved in multiple roles and its exact effects will need to be further substantiated.8Whafs more. IGFBP-rP1 may be closely related with ER-a function. The expression of IGFBP-rP1 is significantly reduced or completely lost in ER-a (+) cell lines, while in some ER-a(-)cell lines, the expression of IGFBP-rP1 is still observed. And in ER-a (-) breast turmors, the expression of IGFBP-rP1 is inversely correlated with the status of proliferation(Ki67).In this study, 5' RACE was applied to get more information about the sequence of B2 in order to see whether B2 was the same gene as IGFBP-rP1. The product of 5' RACE was cloned into T-A vector and white clones were screened by dot blot. Positive clones were selected to sequence. The complete sequence of B2 was achieved by combining the known sequence got by SSH with the sequence from 5'RACE product It shared 98% identity with the cDNA s...
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