Germline mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. Current evidence demonstrates that mutations in BRCA1 do not directly result in tumor formation, but instead cause genetic instability, subjecting cells to high risks of malignant transformation. In an animal model in which Brca1 is mutated specifically in mammary epithelium, tumorigenesis occurs in mutant glands at low frequency after a long latency. Notably, introduction of a p53-null allele significantly enhanced mammary gland tumor formation in Brca1 conditional mutant mice. These results are consistent with a model that Brca1 is a caretaker gene, whose absence causes genetic instability and triggers further alterations, including inactivation of tumor suppressor genes and/or activation of oncogenes, leading to tumor formation.
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Univ Washington, Dept Med, Seattle, WA 98195 USA
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USAUniv Washington, Dept Med, Seattle, WA 98195 USA
Seo, Aaron
Steinberg-Shemer, Orna
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Schneider Childrens Med Ctr, Hematol Unit, IL-49202 Petah Tiqwa, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, IsraelUniv Washington, Dept Med, Seattle, WA 98195 USA
Steinberg-Shemer, Orna
Unal, Sule
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Hacettepe Univ, Dept Pediat, TR-06100 Ankara, TurkeyUniv Washington, Dept Med, Seattle, WA 98195 USA
Unal, Sule
Casadei, Silvia
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Univ Washington, Dept Med, Seattle, WA 98195 USA
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USAUniv Washington, Dept Med, Seattle, WA 98195 USA
Casadei, Silvia
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Walsh, Tom
Gumruk, Fatma
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Hacettepe Univ, Dept Pediat Hematol, TR-06100 Ankara, TurkeyUniv Washington, Dept Med, Seattle, WA 98195 USA
Gumruk, Fatma
Shalev, Stavit
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Technion Israel Inst Technol, Rappaport Fac Med, IL-3525433 Haifa, IsraelUniv Washington, Dept Med, Seattle, WA 98195 USA
Shalev, Stavit
Shimamura, Akiko
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Boston Childrens Hosp, Canc & Blood Disorders Ctr, Boston, MA 02115 USAUniv Washington, Dept Med, Seattle, WA 98195 USA
Shimamura, Akiko
Akarsu, Nurten Ayse
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Hacettepe Univ, Dept Med Genet, TR-06100 Ankara, TurkeyUniv Washington, Dept Med, Seattle, WA 98195 USA
Akarsu, Nurten Ayse
Tamary, Hannah
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Schneider Childrens Med Ctr, Hematol Unit, IL-49202 Petah Tiqwa, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, IsraelUniv Washington, Dept Med, Seattle, WA 98195 USA
Tamary, Hannah
King, Mary-Claire
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Univ Washington, Dept Med, Seattle, WA 98195 USA
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USAUniv Washington, Dept Med, Seattle, WA 98195 USA
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All India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, IndiaAll India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India
Das, Jhuma
Chandra, Lal
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All India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, IndiaAll India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India
Chandra, Lal
Gandhi, Gauri
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All India Inst Med Sci, Obstet & Gynaecol, Bhopal, IndiaAll India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India
Gandhi, Gauri
Amle, Dnyanesh B.
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All India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India
All India Inst Med Sci, Dept Biochem, MIHAN, Plot 2,Sect 20, Nagpur 441108, Maharashtra, IndiaAll India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India
Amle, Dnyanesh B.
Patnayak, Rachana L.
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All India Inst Med Sci, Dept Biochem, Bhopal, Madhya Pradesh, IndiaAll India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India
Patnayak, Rachana L.
Khurana, Nita
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Maulana Azad Med Coll, Pathol, New Delhi, IndiaAll India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India
Khurana, Nita
Saxena, Alpana
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All India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, IndiaAll India Inst Med Sci, Dept Biochem, Nagpur, Maharashtra, India