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Author Rothberg, Jennifer M.
Title Acidic pericellular ph [electronic resource] : effects on proteolysis and gene expression as determined in 30 models of breast carcinoma / by Jennifer M. Rothberg.
Publication Info. 2013.
Location Call No. Status Notes
 Libraries Electronic Books  Electronic Resource - WSU ETD    AVAIL. ONLINE
Description 163 p. : ill.
Note Advisor: Bonnie F. Sloane.
Thesis Thesis (Ph.D.) -- Wayme State University, 2013.
Summary Among the non-cellular microenvironmental factors that contribute to malignancy of solid tumors is an acidic peritumoral pH. The first objective was to determine if an acidic extracellular pH observed in vivo (i.e., pHe 6.8) affects the activity of proteases, such as cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional cultures. At pHe 6.8 there were increases in pericellular active cysteine cathepsins and in degradation of DQ-collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo. The amount of bound probe decreased in tumors in bicarbonate-treated mice, a treatment previously shown to increase peritumoral pHe and reduce local invasion of the tumors. Our results are consistent with the acid-mediated invasion hypothesis and with a role for cathepsin B in promoting degradation of a basement membrane protein substrate, i.e. type IV collagen, in an acidic peritumoral environment. The second objective was to use a microarray approach to identify significantly altered genes that may be of importance in the response to acidic pH in ductal carcinoma in situ (DCIS). We have found that STAT1-directed signaling is up-regulated in response to acidic pH extracellularly. Its role in altering glycolytic pathways suggests an important role for this transcription factor in the development of an acidic extracellular pH.
Subject Molecular biology
Cellular biology
Added Title Wayne State University thesis (Ph.D.) : Cancer Biology
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