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DTIC ADA418942: The Role of AKT1 in Mammary Tumorigenesis and Trans... |
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by Defense Technical Information Center |
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AKT1 belongs to the AKT/PKB protein-serine kinase family |
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and is the cellular homolog of the v-akt oncogene. Gene |
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amplification and overexpression of AKT are associated |
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with adenocarcionomas of the stomach, breast, ovary, and |
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pancreas. AKT1 is coupled to growth factor-dependent |
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proliferation and resistance to apoptosis, but these |
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processes have not been studied in either mammary |
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epithelial cells or in breast cancer. The broad |
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objectives of this proposal are to determine the role of |
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the AKT1 in the proliferation, survival and |
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transformation of mammary epithelial cells using two |
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transgenic mouse strains in which expression of either |
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AKT1 or a constitutively active form of AKT1 is directed |
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to the mammary gland under the control of a mammary gland- |
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specific promoter. The use of these two transgenic models |
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will allow determination of the role of AKT1 in mammary |
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gland hyperplasia, dysplasia and tumorigenesis, and will |
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address the hypothesis that AKT1 is involved in the |
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growth, survival, and transformation of mammary |
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epithelial cells. This hypothesis will be tested using |
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two experimental approaches. First, transgenic mice will |
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be generated with mammary gland-directed expression of |
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wild-type AKT1 or constitutively active myristoylated |
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AKT1 (myrAKT1) to determine their effects on mammary |
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hyperplasia and tumorigenesis. Second, primary mouse |
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mammary epithelial cells will be transduced with |
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ecotropic retroviruses expressing either AKT1 or myrAKT1 |
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to determine their impact on growth factor-dependent |
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proliferation, susceptibility to apoptosis induced by |
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serum deprivation or the P13K inhibitor, LY294002, as |
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well as transformation determined by anchorage- |
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independent growth in soft agar and tumor formation in |
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nude mice. Gene arrays of suppression subtractive |
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hybridization will be used to identify genes modulated by |
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AKT1 that are involved in its anti-apoptotic and |
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proliferative activities. |
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Date Published: 2018-05-14 23:25:53 |
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Identifier: DTIC_ADA418942 |
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Item Size: 65432357 |
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Language: english |
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Media Type: texts |
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# Topics |
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DTIC Archive; Glazer, Robert I ; GEOR... |
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