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Keywords
(15)
Cell Line
Developing Country
Differential Expression
Extracellular Matrix
Immunohistochemi...
Lung Carcinoma
Patient Survival
Predictive Factor
Transforming Growth Factor Beta
Tumor Cells
Adaptor Protein
Full Length
Inducible Protein
Lung Cancer
Tumor Suppressor Gene
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TGFBI expression is associated with a better response to chemotherapy in NSCLC
TGFBI expression is associated with a better response to chemotherapy in NSCLC,10.1186/1476-4598-9-130,Molecular Cancer,Marta Irigoyen,María J Pajares
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TGFBI expression is associated with a better response to chemotherapy in NSCLC
(
Citations: 2
)
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Marta Irigoyen
,
María J Pajares
,
Jackeline Agorreta
,
Mariano Ponz-Sarvisé
,
Elisabeth Salvo
,
María D Lozano
,
Ruben Pío
,
Ignacio Gil-Bazo
,
Ana Rouzaut
BACKGROUND:
Lung cancer
is one of the most prevalent neoplasias in developed countries. Advances in
patient survival
have been limited and the identification of prognostic molecules is needed. Resistance to treatment is strongly related to tumor
cell adhesion
to the
extracellular matrix
and alterations in the quantity and nature of molecules constituting the tumor cell niche. Recently,
transforming growth factor
beta-induced protein (TGFBI), an
extracellular matrix
adaptor protein, has been reported to be differentially expressed in transformed tissues. Loss of TGFBI expression has been described in several cancers including lung carcinoma, and it has been suggested to act as a
tumor suppressor
gene. RESULTS: To address the importance of TGFBI expression in cancer progression, we determined its expression in NSCLC clinical samples using immunohistochemistry. We identified a strong association between elevated TGFBI expression and the response to chemotherapy. Furthermore, we transiently over-expressed and silenced TGFBI in human NSCLC cell lines. Cells over-expressing TGFBI displayed increased sensitivity to etoposide, paclitaxel, cisplatin and gemcitabine. We observed that TGFBI-mediated induction of apoptosis occurred through its binding to αvβ3 integrin. We also determined that full-length TGFBI did not induce caspase 3/7 activation but its proteolytic fragments that were < 3 kDa in size, were able to activate caspase 3, 7 and 8. This pro-apoptotic effect was blocked by anti-αvβ3 integrin antibodies. CONCLUSIONS: The results shown here indicate that TGFBI is a
predictive factor
of the response to chemotherapy, and suggest the use of TGFBI-derived peptides as possible therapeutic adjuvants for the enhancement of responses to chemotherapy.
Journal:
Molecular Cancer - MOL CANCER
, vol. 9, no. 1, pp. 130-12, 2010
DOI:
10.1186/1476-4598-9-130
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Citations
(2)
Comparative study of structural and semiconducting properties of passive films and thermally grown oxides on AISI 304 stainless steel
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