Abstract

The proliferation of estrogen (E)-sensitive human breast tumor cells (MCF7, T47D) in an """"""""in animal-in culture"""""""" system is the central issue studied in this lab. The effect of estradiol-17 beta (E?2?) on specific protein synthesis and its relation with the proliferation of these E?2? target cells is being characterized. These cells carry estrophilins and multiply faster in nude mice to which E?2? is administered than in those in which E?2? is lacking. In culture conditions, charcoal-dextran stripped human sera inhibit the proliferation of these cells in dose-dependent pattern; estrogens cancel this inhibition. These and additional data are compatible with the notion of an indirect and negative control of the proliferation of E?2?-sensitive cells.
The specific aims of this grant are to purify the specific inhibitors of the proliferation of E?2?-sensitive human cells (estrocolyones) and determine the effect of triphenylethylenes (""""""""antiestrogens"""""""") on the proliferation of the above mentioned cells within the context of the indirect and direct negative control paradigm. (D)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA013410-13
Application #
3163763
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1976-06-01
Project End
1989-12-31
Budget Start
1986-03-01
Budget End
1986-12-31
Support Year
13
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Soto, Ana M; Maffini, Maricel V; Schaeberle, Cheryl M et al. (2006) Strengths and weaknesses of in vitro assays for estrogenic and androgenic activity. Best Pract Res Clin Endocrinol Metab 20:15-33
Soto, Ana M; Sonnenschein, Carlos (2004) The somatic mutation theory of cancer: growing problems with the paradigm? Bioessays 26:1097-107
Powell, Charles E; Soto, Ana M; Michaelson, Cheryl L et al. (2003) Characterization of a plasma membrane-resident albumin-binding protein associated with the proliferation of estrogen-target, serum-sensitive cells. Steroids 68:487-96
Maffini, Maricel V; Geck, Peter; Powell, Charles E et al. (2002) Mechanism of androgen action on cell proliferation: AS3 protein as a mediator of proliferative arrest in the rat prostate. Endocrinology 143:2708-14
Powell, C E; Soto, A M; Sonnenschein, C (2001) Identification and characterization of membrane estrogen receptor from MCF7 estrogen-target cells. J Steroid Biochem Mol Biol 77:97-108
Sonnenschein, C; Soto, A M (2000) Somatic mutation theory of carcinogenesis: why it should be dropped and replaced. Mol Carcinog 29:205-11
Geck, P; Maffini, M V; Szelei, J et al. (2000) Androgen-induced proliferative quiescence in prostate cancer cells: the role of AS3 as its mediator. Proc Natl Acad Sci U S A 97:10185-90
Szelei, J; Soto, A M; Geck, P et al. (2000) Identification of human estrogen-inducible transcripts that potentially mediate the apoptotic response in breast cancer. J Steroid Biochem Mol Biol 72:89-102
Geck, P; Szelei, J; Jimenez, J et al. (1999) Early gene expression during androgen-induced inhibition of proliferation of prostate cancer cells: a new suppressor candidate on chromosome 13, in the BRCA2-Rb1 locus. J Steroid Biochem Mol Biol 68:41-50
Soto, A M; Michaelson, C L; Prechtl, N V et al. (1998) Assays to measure estrogen and androgen agonists and antagonists. Adv Exp Med Biol 444:9-23;discussion 23-8

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