| Breast cancer is the most common internal malignancy affecting women. Despite advances in surgery, chemotherapy, and radiotherapy, breast cancer remains a major cause of morbidity and mortality. As a result, the search continues for sensitive and selective markers for the early detection of beast cancer, better prognostic indicators, and novel targets for new anticancer therapies. The pathogenesis responsible for breast cancer is not well understood. However, numerous oncogenic and tumor suppressor proteins such as EGFR, erB family, c-jun, c-myc et al. have been implicated as members of signal regulatory pathways controlling cell growth and differentiationThe biochemical abnormalities of signal pathways have been considered as one of the most important mechanisms underlying malignant transformation. Among them, PI3-K pathway and MAPK pathway have been implicated central roles in the mitogenic pathways regulating cell growth, proliferation, differentiation and transformation and thus involved in tumorigenesis. Moreover, Cross talk between PI3-K pathway and MAPK pathway is mediated by direct phosphorylation and inactivation of the conservative site of Raf of MAPK pathway by Akt of PI3-K pathway, which leads to the inhibition of MAPK pathway. PI3-K and Erk2, important members of PI3-K pathway and MAPK pathway, respectively, can translocate to nucleus from cytoplasm by the diverse mitogenic stimuli on cell membrane, then activate some related transcription factor and regulate the transcription of oncogenes. So both PI3-K and Erk2 are considered as important factors in tumorigenesis.In this article, we examined the protein, activity and mRNA levels of both Erk2 and PI3-K in a series of breast tumors and adjacent mammary glands collected at surgery, including 37 cases of breast cancer, 6 cases of atypicalhyperplasia-breast carcinoma in situ and 15 cases of benigh conditions. The purpose is to figure out the changes of Erk2 and PI3-K during the dynamic process of breast tumorigenesis and thus the roles of both PI3-K pathway and MAPK pathway. Western blot, kinase activity assay and RT-PCR were employed to detect the protein expression, kinase activity and mRNA level, respectively.PI3-K is a heterodimer comprised of a 85-kDa adaptor subunit (p85) and a 110-kDa catalytic subunit (pi 10). Little is known about the involvement PI3-K in human breast cancer with the exception of the report on the increased expression of p85 subunit of PI3-K. Therefore, for the first time, we investigate the protein, kinase activity and mRNA levels of PI3-K during the different stages of breast cancer, including adjacent normal tissue - benigh condition-atypical hyperplasia-cancinoma in situ - breast cancer as the first part of the article. The protein level was studied by Western blot. The phosphotransferase activity of PI3-K was detected by kinase activity assay using PI as a substrate after purification through immunoprecipitation. RT-PCR was utilized to examine the mRNA level. Not only the protein expression but also the kinase activity and mRNA expression of PI3-K have shown elevated levels in beast cancer, while no obvious enhanced levels were found during the other conditions. These findings suggest that PI3-K was activated in breast cancer. PI3-K may play an important role at the stage of breast cancer progression. PI3-K pathway may be involved in the signal transduction during the progression of breast cancer.Recent work has defined the increased levels of the protein expression, kinase activity and mRNA expression by in situ RT-PCR in breast cancer. For furthering our understanding of the role of Erk2 in breast tumorigenesis, we studied the changes of Erk2 during the dynamic process of breast tumorigenesis for the first time as the second part of the article. Western blot was used to determine the Erk2 protein level at the various stages of breast cancer, includingadjacent normal mammary glands, benigh lesion, atypical hyperplasia-in situ carcinoma and invasive breast cancer. The order among these differ...
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