The purpose of this project is to investigate molecular mechanisms involved in the response of cells to hyperthermia. We will concentrate on determining the effect of clinically relevant hyperthermia doses an the functions of membrane enzyme systems involved in transmembrane signaling. Our preliminary data indicates that hyperthermia produces rapid and profound stimulation of the 3 major such systems. These are the adenylate cyclase, phospholipase C and phospholipase A2 systems. As these signaling systems are intimately involved in regulating all of the major functions of cells (proliferation, differentiation, metabolism, etc.) Their stimulation by hyperthermia may be highly significant. We will investigate the hypothesis that activation of transmembrane signal pathways generates cascade responses at the plasma membrane. These cascade responses may then be involved in mediating thermal cell killing, inducing thermotolerance and modulating tumor blood flow and cellular radiosensitivity. We will additionally examine the hypothesis that a common component of all signal transduction systems, the guanine nucleotide binding protein, constitutes a universal target for hyperthermia.
We aim to test the possibility that these proteins may serve as transducers of the physical effects of hyperthermia just as they transduce the chemical messages of hormones and other signalling agonists.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA047407-03
Application #
3191052
Study Section
Radiation Study Section (RAD)
Project Start
1988-05-01
Project End
1993-04-30
Budget Start
1990-05-01
Budget End
1991-04-30
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
Murshid, Ayesha; Theriault, Jimmy; Gong, Jianlin et al. (2018) Molecular Chaperone Receptors. Methods Mol Biol 1709:331-344
Murshid, Ayesha; Prince, Thomas L; Lang, Ben et al. (2018) Role of Heat Shock Factors in Stress-Induced Transcription. Methods Mol Biol 1709:23-34
Eguchi, Takanori; Calderwood, Stuart K; Takigawa, Masaharu et al. (2017) Intracellular MMP3 Promotes HSP Gene Expression in Collaboration With Chromobox Proteins. J Cell Biochem 118:43-51
Calderwood, Stuart K; Gong, Jianlin (2016) Heat Shock Proteins Promote Cancer: It's a Protection Racket. Trends Biochem Sci 41:311-323
Calderwood, Stuart K; Neckers, Len (2016) Hsp90 in Cancer: Transcriptional Roles in the Nucleus. Adv Cancer Res 129:89-106
Gong, J; Weng, D; Eguchi, T et al. (2015) Targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis. Oncogene 34:5460-71
Bunch, Heeyoun; Lawney, Brian P; Lin, Yu-Fen et al. (2015) Transcriptional elongation requires DNA break-induced signalling. Nat Commun 6:10191
Murshid, Ayesha; Gong, Jianlin; Prince, Thomas et al. (2015) Scavenger receptor SREC-I mediated entry of TLR4 into lipid microdomains and triggered inflammatory cytokine release in RAW 264.7 cells upon LPS activation. PLoS One 10:e0122529
Murshid, Ayesha; Gong, Jianlin; Ahmad, Ridwan et al. (2015) Scavenger receptor SREC-I promotes double stranded RNA-mediated TLR3 activation in human monocytes. Immunobiology 220:823-32
Eguchi, Taka; Prince, Thomas; Wegiel, Barbara et al. (2015) Role and Regulation of Myeloid Zinc Finger Protein 1 in Cancer. J Cell Biochem 116:2146-54

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