Abstract

Somatic cell hybridization studies have clearly demonstrated the phenomenon of suppression of tumorigenicity. We intend to identify the gene(s) involved in tumor suppression and characterize their function. Initially, single chromosome (microcell) transfers will be used to identify specific chromosome(s) that carry the tumor-suppressor gene(s). Subtractive cDNA hybridization procedures will be used to clone these genes. We shall also investigate the interaction between tumor- suppressor gene(s) and oncogenes. The relevant genes will be inserted into expression vectors, containing an inducible MMTV- LTR promoter, in both sense and anti-sense orientations. The effect of varying the level of sense and anti-sense expression of these genes will be examined. We have already identified a candidate recessive oncogene product (p75 tumor antigen). We intend to clone and characterize the gene encoding p75 and investigate its role in tumorigenic behavior of HeLa cells. The trans-acting gene that regulates expression of p75 will also be cloned and characterized. The possibility that this trans-acting regulatory gene is a tumor- suppressor gene will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37CA019401-12
Application #
3481821
Study Section
Pathology B Study Section (PTHB)
Project Start
1976-06-30
Project End
1992-05-31
Budget Start
1987-07-01
Budget End
1988-05-31
Support Year
12
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Liao, S-Y; Ivanov, S; Ivanova, A et al. (2003) Expression of cell surface transmembrane carbonic anhydrase genes CA9 and CA12 in the human eye: overexpression of CA12 (CAXII) in glaucoma. J Med Genet 40:257-61
Kaluz, Stefan; Kaluzova, Milota; Chrastina, Adrian et al. (2002) Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor 1 alpha stabilization: a role for phosphatidylinositol 3'-kinase. Cancer Res 62:4469-77
Cheng, Yue; Chakrabarti, Rita; Garcia-Barcelo, Merce et al. (2002) Mapping of nasopharyngeal carcinoma tumor-suppressive activity to a 1.8-megabase region of chromosome band 11q13. Genes Chromosomes Cancer 34:97-103
Srivatsan, Eri S; Chakrabarti, Rita; Zainabadi, Kayvan et al. (2002) Localization of deletion to a 300 Kb interval of chromosome 11q13 in cervical cancer. Oncogene 21:5631-42
Ivanov, S; Liao, S Y; Ivanova, A et al. (2001) Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Am J Pathol 158:905-19
Kong, X T; Gao, H; Stanbridge, E J (2001) Mechanisms of differential activation of target gene promoters by p53 hinge domain mutants with impaired apoptotic function. J Biol Chem 276:32990-3000
Kaluzova, M; Pastorekova, S; Svastova, E et al. (2001) Characterization of the MN/CA 9 promoter proximal region: a role for specificity protein (SP) and activator protein 1 (AP1) factors. Biochem J 359:669-77
Tsujimoto, H; Nishizuka, S; Redpath, L J et al. (2001) Examination of the oncogenic potential of H19 gene in HeLa x normal human fibroblast hybrid cells. Int J Oncol 19:89-95
Olive, P L; Aquino-Parsons, C; MacPhail, S H et al. (2001) Carbonic anhydrase 9 as an endogenous marker for hypoxic cells in cervical cancer. Cancer Res 61:8924-9
Srivatsan, E S; Bengtsson, U; Manickam, P et al. (2000) Interstitial deletion of 11q13 sequences in HeLa cells. Genes Chromosomes Cancer 29:157-65

Showing the most recent 10 out of 57 publications