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DTIC ADA386500: Analysis of Multistep Mammary Tumorigenesis in Wnt-... |
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by Defense Technical Information Center |
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Breast cancer like all cancers, is a multi step process |
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involving the sequential acquisition of genetic |
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alterations over a period of time. Studying this process |
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in humans is a prolonged and arduous task; therefore, |
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animal models are a desirable alternative. We have used a |
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Wntl transgenic mouse model to study the multiple genetic |
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events in mammary cancer development. We infected these |
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transgenic mice with the mouse mammary tumor virus (MMTV) |
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to accelerate tumorigenesis and to molecularly tag proto- |
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oncogenes that are activated in the resulting tumors and |
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that cooperate with Wnt- 1 in mammary tumorigenesis. By |
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examination of the tumors that lack activation of genes |
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that are usual targets of MMTV insertions, we identified |
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a common insertion locus for MMTV and determined the |
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activated gene in this locus to be another member of the |
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FGF family, Fgf8/8. Fgf8 is transcriptionaly activated in |
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50% of the tumors from infected Wntl transgenic mice in |
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comparison to the lack of Fgf8 RNA in other tumors and |
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mammary tissues, suggesting a strong oncogenic |
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cooperation between Fgf8 and Wntl in mammary |
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tumorigenesis. Fgf8 induced apoptosis of mammary |
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epithelial cells as evidenced by nuclear condensation and |
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fragmentation and oligonucleosomal laddering. |
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Overexpression of the anti-apoptotic gene bcl2 in these |
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cells transiently rescued or delayed the apoptosis |
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induced by FGFs. These results describe a new property |
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for FGFs and suggest that these growth factors play very |
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important roles in regulating cell growth and death both |
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in normal development as well as in pathological |
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conditions like cancer. |
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Date Published: 2018-04-30 23:05:12 |
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Identifier: DTIC_ADA386500 |
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Item Size: 103918337 |
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Language: english |
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Media Type: texts |
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# Topics |
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DTIC Archive; Shankar, Deepa; CHILDRE... |
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