Abstract

The ability of neoplastic cells to initiate DNA synthesis and proliferate in Ca2+-deficient medium distinguishes them from their non-neoplastic counterparts. A clue to understanding this alteration is the fact that tumor promoting agents enable non-neoplastic rat liver epithelial cells to initiate DNA synthesis and proliferate in Ca2+-deficient medium like their neoplastic counterparts. It follows that uncovering the mechanisms responsible for this phenomenon should not only enhance our knowledge of the neoplastic process but also provide opportunities to modulate the tumor promotion process. These are our long range objectives. This proposal will test the hypothesis that tumor promoters in general stimulate Ca2+-deprived rat liver cells to initiate DNA synthesis through a mechanism involving Ca2+-calmodulin, cyclic AMP, cyclic AMP-dependent protein kinases and Ca2+/phospholipid-dependent protein kinase activity. The cell surface and intracellular phosphoprotein substrates will be identified and their requirement for DNA-synthetic activity and tumor promotion determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039745-03
Application #
3179135
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1985-08-01
Project End
1988-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Hawaii
Department
Type
Organized Research Units
DUNS #
121911077
City
Honolulu
State
HI
Country
United States
Zip Code
96822

  Publications

Messner, Donald J; Romeo, Charles; Boynton, Alton et al. (2006) Inhibition of PP2A, but not PP5, mediates p53 activation by low levels of okadaic acid in rat liver epithelial cells. J Cell Biochem 99:241-55
Huang, Ruochun; Lin, Ying; Wang, Cheng C et al. (2002) Connexin 43 suppresses human glioblastoma cell growth by down-regulation of monocyte chemotactic protein 1, as discovered using protein array technology. Cancer Res 62:2806-12
Huang, R P; Hossain, M Z; Huang, R et al. (2001) Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells. Int J Cancer 92:130-8
Huang, R P; Peng, A; Golard, A et al. (2001) Hydrogen peroxide promotes transformation of rat liver non-neoplastic epithelial cells through activation of epidermal growth factor receptor. Mol Carcinog 30:209-17
Messner, D J; Ao, P; Jagdale, A B et al. (2001) Abbreviated cell cycle progression induced by the serine/threonine protein phosphatase inhibitor okadaic acid at concentrations that promote neoplastic transformation. Carcinogenesis 22:1163-72
Huang, R; Liu, Y G; Lin, Y et al. (2001) Enhanced apoptosis under low serum conditions in human glioblastoma cells by connexin 43 (Cx43). Mol Carcinog 32:128-38
Tamura, K; Rice, R L; Wipf, P et al. (1999) Dual G1 and G2/M phase inhibition by SC-alpha alpha delta 9, a combinatorially derived Cdc25 phosphatase inhibitor. Oncogene 18:6989-96
Huang, R P; Fan, Y; Boynton, A L (1999) UV irradiation upregulates Egr-1 expression at transcription level. J Cell Biochem 73:227-36
Huang, R P; Hossain, M Z; Sehgal, A et al. (1999) Reduced connexin43 expression in high-grade human brain glioma cells. J Surg Oncol 70:21-4
Huang, R P; Peng, A; Hossain, M Z et al. (1999) Tumor promotion by hydrogen peroxide in rat liver epithelial cells. Carcinogenesis 20:485-92

Showing the most recent 10 out of 32 publications