Abstract

This project is designed to characterize the potential for differentiation therapy based on molecular mechanisms of differentiation promoters acting on human colon carcinoma. Preliminary observations in a well-characterized system of colonic carcinoma cell lines with diverse biological properties (Brattain et al., 1984) and results obtained in their response to various differentiation promoters, have led us to the hypothesis that the induction of extracellular matrix (ECM) components is a critical step in the differentiation process. Cellular ECM's individual ECM components and combinations of ECM components will be assessed for their ability to induce differentiation responses. Combinations of differentiation promoters, ECM and individual components will be characterized for their ability to enhance the differentiation of partially responsive or completely unresponsive lines to individual differentiation promoting agents. Differentiation and growth control have been closely linked to the expression of autocrine growth factors. It is not known how ECM or ECM components will affect the expression of these genes, but ECM has been shown specifically to induce the expression of differentiated products such as casein in cultured mammary cells. Expression of mRNA's for a stimulatory autocrine factor (transforming growth factor-a) and an inhibitory autocrine factor (transforming growth factor-B) as a function of ECM induced differentiation will be characterized.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050457-02
Application #
3194944
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1989-12-01
Project End
1992-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Sawhney, Rajinder S; Liu, Wensheng; Brattain, Michael G (2009) A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via Fak signaling. J Cell Physiol 219:152-61
Sawhney, Rajinder S; Cookson, Michelle M; Omar, Yasin et al. (2006) Integrin alpha2-mediated ERK and calpain activation play a critical role in cell adhesion and motility via focal adhesion kinase signaling: identification of a novel signaling pathway. J Biol Chem 281:8497-510
Ammanamanchi, Sudhakar; Tillekeratne, Manoranjani P M; Ko, Tien C et al. (2004) Endogenous control of cell cycle progression by autocrine transforming growth factor beta in breast cancer cells. Cancer Res 64:2509-15
Wang, Jing; Sergina, Natalia; Ko, Tien C et al. (2004) Autocrine and exogenous transforming growth factor beta control cell cycle inhibition through pathways with different sensitivity. J Biol Chem 279:40237-44
Sawhney, Rajinder S; Cookson, Michelle M; Sharma, Bhavya et al. (2004) Autocrine transforming growth factor alpha regulates cell adhesion by multiple signaling via specific phosphorylation sites of p70S6 kinase in colon cancer cells. J Biol Chem 279:47379-90
Ammanamanchi, Sudhakar; Freeman, James W; Brattain, Michael G (2003) Acetylated sp3 is a transcriptional activator. J Biol Chem 278:35775-80
Gong, JianGen; Ammanamanchi, Sudhakar; Ko, Tien C et al. (2003) Transforming growth factor beta 1 increases the stability of p21/WAF1/CIP1 protein and inhibits CDK2 kinase activity in human colon carcinoma FET cells. Cancer Res 63:3340-6
Bandyopadhyay, Abhik; Zhu, Yong; Malik, Shazli N et al. (2002) Extracellular domain of TGFbeta type III receptor inhibits angiogenesis and tumor growth in human cancer cells. Oncogene 21:3541-51
Sawhney, Rajinder S; Zhou, Guo-Hao K; Humphrey, Lisa E et al. (2002) Differences in sensitivity of biological functions mediated by epidermal growth factor receptor activation with respect to endogenous and exogenous ligands. J Biol Chem 277:75-86
Yang, L; Yang, J; Venkateswarlu, S et al. (2001) Autocrine TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in breast cells. J Cell Physiol 188:383-93

Showing the most recent 10 out of 37 publications