Linked Life Data

21617856

Source:http://linkedlifedata.com/resource/pubmed/id/21617856

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-6-13
pubmed:abstractText
Drug resistance causes treatment failure in approximately 50% of breast cancer patients with chemotherapy. Overexpression of glucosylceramide synthase (GCS) confers drug resistance in cancer cells, and suppression of GCS sensitizes cancers to chemotherapy in preclinical studies. Thus, GCS becomes a potential target to reverse drug resistance; however, little is known about GCS expression levels in normal tissues and whether GCS overexpression is associated with metastatic cancers. Herewith, we report our studies in GCS expression levels and breast cancer from patients. GCS levels were analyzed using cancer profiling arrays, breast cancer histo-arrays and quantitative RT-PCR in tumor tissues. We found that breast (18 exp. index) and other hormone-dependent organs (testis, cervix, ovary, prostate) displayed the lowest levels of GCS mRNA, whereas liver (52 exp. index) and other organs (kidney, bladder, stomach) displayed the highest levels of GCS. GCS mRNA levels were significantly elevated in tumors of breast, cervix, rectum and small intestine, as compared to each paired normal tissue. In mammary tissue, GCS overexpression was detected in breast cancers with metastasis, but not in benign fibroadenoma or primary tumors. GCS overexpression was coincident with HER2 expression (?2=0.84) in ER-negative breast adenocarcinoma. In tumor specimens, GCS mRNA was elevated by 4-fold and significantly associated with stage III (5/7), lymph node-positive (7/8) and estrogen receptor-positive breast cancers (7/9). GCS expression was significantly and selectively elevated in breast cancer, in particular in metastatic disease. GCS overexpression was highly associated with ER-positive and HER2-positive breast cancer with metastasis. Although a small study, these data suggest that GCS may be a prognostic indicator and potential target for the treatment of chemotherapy-refractory breast cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
425-31
pubmed:meshHeading
pubmed-meshheading:21617856-Adult, pubmed-meshheading:21617856-Aged, pubmed-meshheading:21617856-Breast Neoplasms, pubmed-meshheading:21617856-Cell Line, Tumor, pubmed-meshheading:21617856-Disease Progression, pubmed-meshheading:21617856-Drug Resistance, Neoplasm, pubmed-meshheading:21617856-Female, pubmed-meshheading:21617856-Gene Expression Profiling, pubmed-meshheading:21617856-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21617856-Glucosyltransferases, pubmed-meshheading:21617856-HL-60 Cells, pubmed-meshheading:21617856-HeLa Cells, pubmed-meshheading:21617856-Humans, pubmed-meshheading:21617856-K562 Cells, pubmed-meshheading:21617856-Middle Aged, pubmed-meshheading:21617856-Neoplasm Staging, pubmed-meshheading:21617856-RNA, Messenger, pubmed-meshheading:21617856-Receptor, erbB-2, pubmed-meshheading:21617856-Receptors, Estrogen, pubmed-meshheading:21617856-Tissue Array Analysis
pubmed:year
2011
pubmed:articleTitle
Glucosylceramide synthase, a factor in modulating drug resistance, is overexpressed in metastatic breast carcinoma.
pubmed:affiliation
Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA. yliu@ulm.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural