A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers.

Brittney Shea Herbert, Rebecca A. Chanoux, Yunlong Liu, Peter H. Baenziger, Chirayu P. Goswami, Jeanette McClintick, Howard J. Edenberg, Robert E. Pennington, Steven M. Lipkin, Levy Kopelovich

Research output: Contribution to journalArticle

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Abstract

Specific changes in gene expression during cancer initiation should enable discovery of biomarkers for risk assessment, early detection and targets for chemoprevention. It has been previously demonstrated that altered mRNA and proteome signatures of morphologically normal cells bearing a single inherited "hit" in a tumor suppressor gene parallel many changes observed in the corresponding sporadic cancer. Here, we report on the global gene expression profile of morphologically normal, cultured primary breast epithelial and stromal cells from Li-Fraumeni syndrome (LFS) TP53 mutation carriers. Our analyses identified multiple changes in gene expression in both morphologically normal breast epithelial and stromal cells associated with TP53 haploinsufficiency, as well as interlocking pathways. Notably, a dysregulated p53 signaling pathway was readily detectable. Pharmacological intervention with the p53 rescue compounds CP-31398 and PRIMA-1 provided further evidence in support of the central role of p53 in affecting these changes in LFS cells and treatment for this cancer. Because loss of signaling mediated by TP53 is associated with the development and survival of many human tumors, identification of gene expression profiles in morphologically normal cells that carry "one-hit" p53 mutations may reveal novel biomarkers, enabling the discovery of potential targets for chemoprevention of sporadic tumors as well.

Original languageEnglish
Pages (from-to)405-422
Number of pages18
JournalOncotarget
Volume1
Issue number6
StatePublished - Oct 2010

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Li-Fraumeni Syndrome
Stromal Cells
Breast
Epithelial Cells
Mutation
Chemoprevention
Neoplasms
Transcriptome
Biomarkers
Gene Expression
Haploinsufficiency
Forensic Anthropology
Proteome
Tumor Suppressor Genes
Pharmacology
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Herbert, B. S., Chanoux, R. A., Liu, Y., Baenziger, P. H., Goswami, C. P., McClintick, J., ... Kopelovich, L. (2010). A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers. Oncotarget, 1(6), 405-422.

A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers. / Herbert, Brittney Shea; Chanoux, Rebecca A.; Liu, Yunlong; Baenziger, Peter H.; Goswami, Chirayu P.; McClintick, Jeanette; Edenberg, Howard J.; Pennington, Robert E.; Lipkin, Steven M.; Kopelovich, Levy.

In: Oncotarget, Vol. 1, No. 6, 10.2010, p. 405-422.

Research output: Contribution to journalArticle

Herbert, BS, Chanoux, RA, Liu, Y, Baenziger, PH, Goswami, CP, McClintick, J, Edenberg, HJ, Pennington, RE, Lipkin, SM & Kopelovich, L 2010, 'A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers.', Oncotarget, vol. 1, no. 6, pp. 405-422.
Herbert, Brittney Shea ; Chanoux, Rebecca A. ; Liu, Yunlong ; Baenziger, Peter H. ; Goswami, Chirayu P. ; McClintick, Jeanette ; Edenberg, Howard J. ; Pennington, Robert E. ; Lipkin, Steven M. ; Kopelovich, Levy. / A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers. In: Oncotarget. 2010 ; Vol. 1, No. 6. pp. 405-422.
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