The Possible Role of E2F in Rat Mammary Carcinogenesis.
Abstract
E2F transcription factors are believed to control cell growth by being downstream targets of G1 cyclins and the retinoblastoma (Rb) tumor suppressor family. Overexpression and deletion studies in tissue culture and in vivo indicate that many E2Fs play a critical role in growth regulation. Since G1 cyclins are upregulated or disregulated and Rb is mutated in several cancers, particularly in breast cancer, upregulation of E2F activity is implicated in cancer development. In order to determine if E2F upregulation is involved in mammary tumorigenesis, retroviruses overexpressing E2F4 were infused into rat mammary glands. No palpable mammary tumors have arisen during five months. Since E2F4 did not cause tumors when overexpressed by itself, a retroviral vector that coexpressed E2F4 and an activated form of c-Ha-ras was made. ras is a known initiator of mammary carcinomas. If E2F plays a role in the progression stage of cancer, the contribution of E2F to cancer development should be more apparent when coexpressed with ras. In addition, coexpression of ras with a dominant negative form of E2F (an E2F with a mutated DNA binding domain) will determine whether ras initiated carcinogenesis is dependent on an E2F pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1997
- Accession Number
- ADA332877
Entities
People
- Peggy J. Farnham
- Traci Lee
Organizations
- University of Wisconsin–Madison