Abstract

The long term goals are to identify the changes in the program of cellular gene expression induced by the 12S gene that results in primary-epithelial cell immortalization and the mechanism(s) by which they occur. Knowing how a cell becomes immortalized is important for our ultimate understanding of the multistep conversion of a normal cell to the tumorigenic transformed phenotype. Although most human neoplasms are of epithelial origin, very little is known about their transformation. Since the 12S gene specifically affects this cell type, it provides a means to study then progression at the cellular and molecular level. Much is known about the first exon of 12S, therefore the investigator will concentrate on the second exon, whose expression is also required for immortalization. The investigator will perform a detailed genetic analysis of the second exon to determine which region(s) and function(s) are important for immortalization. Cellular genes whose expression is modulated by the presence of this region, will be identified.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050540-05
Application #
2093843
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1990-06-01
Project End
1996-05-31
Budget Start
1994-06-01
Budget End
1996-05-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Tennessee Health Science Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163

  Publications

Gopalakrishnan, S; Douglas, J L; Quinlan, M P (1997) Immortalization of primary epithelial cells by E1A 12S requires late, second exon-encoded functions in addition to complex formation with pRB and p300. Cell Growth Differ 8:541-51
Malladi, A; Quinlan, M P (1997) Mutations in CR1 of E1A 12S yield dominant negative suppressors of immortalization and the lytic cycle. Virology 233:51-62
Gopalakrishnan, S; Fischer, R S; Quinlan, M P (1996) Induction of a complex between rasGAP and a novel 110 kD protein is required for immortalization of primary epithelial cells by the E1A 12S oncoprotein of adenovirus. Oncogene 13:2659-69
Douglas, J L; Quinlan, M P (1996) Structural limitations of the Ad5 E1A 12S nuclear localization signal. Virology 220:339-49
Krantz, C K; Routes, B A; Quinlan, M P et al. (1996) E1A second exon requirements for induction of target cell susceptibility to lysis by natural killer cells: implications for the mechanism of action. Virology 217:23-32
Douglas, J L; Quinlan, M P (1995) Efficient nuclear localization and immortalizing ability, two functions dependent on the adenovirus type 5 (Ad5) E1A second exon, are necessary for cotransformation with Ad5 E1B but not with T24ras. J Virol 69:8061-5
Gopalakrishnan, S; Quinlan, M P (1995) Modulation of E-cadherin localization in cells expressing wild-type E1A 12S or hypertransforming mutants. Cell Growth Differ 6:985-98
Quinlan, M P (1994) Enhanced proliferation, growth factor induction and immortalization by adenovirus E1A 12S in the absence of E1B. Oncogene 9:2639-47
Douglas, J L; Quinlan, M P (1994) Efficient nuclear localization of the Ad5 E1A 12S protein is necessary for immortalization but not cotransformation of primary epithelial cells. Cell Growth Differ 5:475-83
Quinlan, M P (1993) Expression of antisense E1A in 293 cells results in altered cell morphologies and cessation of proliferation. Oncogene 8:257-65

Showing the most recent 10 out of 11 publications