Breast cancer is the most common cancer of women in the western world. Breast cancer patients do not die of their primary breast lesions, they die of metastatic disease, and this application will address the role of differentially expressed genes in the progression of breast cancer. Since none of the known genetic markers alone is a better prognostic indicator than tumor size and nodal status, we will collectively examine a number of genes that are related to tumor progression. In preliminary studies we have identified.several genes that are differentially expressed in highly metastatic rat mammary carcinoma cell lines. Some of the differentially expressed genes in highly.metastatic rat mammary cells have been partially sequenced and identified as cytokeritans, degradative enzymes, calcium-binding proteins, transcription factors- elongation factors, and mitogen-activated proteins. In some cases we have independent evidence for the involvement of certain gene products (annexins, cytokeritans, degradative enzymes) in the malignant properties of highly metastatic cells. The role of the other identified genes in conferring malignant characteristics and a functional conformation of the known genes in metastatic properties will be examined by transfection of full-length cDNAs or antisense constructs into recipient stable, benign or metastatic cells followed by assays for altered in vitro or in vivo properties, such as those involved in adhesion, invasion, growth, or metastasis. For example, we will measure adhesion to microvessel endothelial cells, invasion of extracellular matrix, response to paracrine motility and growth factors, and metastatic properties in F344 rats or nude (nu/nu) mice. Other cDNAs that we have isolated and sequenced are over- or under-expressed in metastatic mammary cells and are not homologous to any known gene. We will complete the sequencing of these genes and obtain full length cDNAs. Candidate full-length cDNAs will be transfected into recipient benign or highly metastatic cells, and we will test for changes in malignant cell properties. 'We will then examine if the expression of the candidate metastasis-associated gene products in clinical biopsies, including primary and secondary breast carcinomas, benign adenomas and other neoplastic and non-neoplastic lesions, predict the likelihood of recurrence of breast cancers at regional or distant sites. The goals of this project are to establish new genetic markers for metastasis and recurrence of breast cancer, identify genes whose differential expression is important in metastasis, and learn more about how multiple changes in gene expression confer the malignant and metastatic phenotype.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA063045-01
Application #
2104641
Study Section
Pathology B Study Section (PTHB)
Project Start
1994-05-01
Project End
1997-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Biology
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Hoeppner, Bettina B; Redding, Colleen A; Rossi, Joseph S et al. (2012) Factor structure of decisional balance and temptations scales for smoking: cross-validation in urban female African-American adolescents. Int J Behav Med 19:217-27
Velicer, Wayne F; Prochaska, James O; Redding, Colleen A (2006) Tailored communications for smoking cessation: past successes and future directions. Drug Alcohol Rev 25:49-57
Ward, Rose Marie; Velicer, Wayne F; Rossi, Joseph S et al. (2004) Factorial invariance and internal consistency for the decisional balance inventory--short form. Addict Behav 29:953-8
Velicer, Wayne F; Prochaska, James O (2004) A comparison of four self-report smoking cessation outcome measures. Addict Behav 29:51-60
Nicolson, Garth L; Nawa, Akihiro; Toh, Yasushi et al. (2003) Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis 20:19-24
Hu, Mei; Nicolson, Garth L; Trent 2nd, Jonathan C et al. (2002) Characterization of 11 human sarcoma cell strains: evaluation of cytogenetics, tumorigenicity, metastasis, and production of angiogenic factors. Cancer 95:1569-76
Plummer, B A; Velicer, W F; Redding, C A et al. (2001) Stage of change, decisional balance, and temptations for smoking: measurement and validation in a large, school-based population of adolescents. Addict Behav 26:551-71
Nawa, A; Nishimori, K; Lin, P et al. (2000) Tumor metastasis-associated human MTA1 gene: its deduced protein sequence, localization, and association with breast cancer cell proliferation using antisense phosphorothioate oligonucleotides. J Cell Biochem 79:202-12
Velicer, W F; Prochaska, J O (1999) An expert system intervention for smoking cessation. Patient Educ Couns 36:119-29
Migneault, J P; Velicer, W F; Prochaska, J O et al. (1999) Decisional balance for immoderate drinking in college students. Subst Use Misuse 34:1325-46

Showing the most recent 10 out of 23 publications