BxPC3 pancreatic cancer cells express a truncated Smad4 protein upon PI3K and mTOR inhibition

April 2014
Oncology Letters;2014, Vol. 7 Issue 4, p1165
Academic Journal
Smad4 is a critical regulator of transforming growth factor (TGF)-β signaling and is defective in numerous human cancers. In total, 30% of pancreatic cancers harbor a homozygous deletion of Smad4. The human pancreatic cancer cell line, BxPC3, has been reported to be Smad4-null due to a homozygous deletion and has been widely used as a Smad4-null model. The present study reports that Smad4 DNA is present in BxPC3 cells, and under conditions of suppressed mammalian target of rapamycin complex 1 (mTORC1) and phosphatidylinositol-3-kinase, a truncated Smad4 protein is expressed. While a high level of Smad4 protein can be expressed in these cells, the cells do not respond to TGF-β. The Smad4 defect in BxPC3 cells likely occurs via translocation rather than deletion as previously reported.


Related Articles

  • Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome. Bellucco, Fernanda T.; Nunes, Natália; Colovati, Mileny E.S.; Malinverni, andréa C.M.; Caneloi, Thamy P.; Soares, Maria F.; a. Perez, ana B.; Melaragno, Maria I. // Cytogenetic & Genome Research;Aug2017, Vol. 152 Issue 1, p29 

    Miller-Dieker syndrome (MDS) is a contiguous gene deletion syndrome in which almost all patients present de novo 17p13.3 deletions. We report on a male infant with MDS and an unusual unbalanced translocation involving chromosomes Y and 17 that resulted in a large 5.5-Mb 17pterp13.2 deletion and...

  • Twist promotes invasion and cisplatin resistance in pancreatic cancer cells through growth differentiation factor 15. HONG JI; HONG-WEI LU; YI-MING LI; LE LU; JIN-LONG WANG; YA-FEI ZHANG; HAO SHANG // Molecular Medicine Reports;2015, Vol. 12 Issue 3, p3841 

    Pancreatic cancer (PC) is an aggressive and devastating disease with a poor prognosis. Cisplatin, a commonly used chemotherapeutic agent for solid tumors, is effective as a single agent or in combination with other drugs for the treatment of PC. Previous studies have suggested that Twist and...

  • Personalizing pancreatic cancer organoids with hPSCs. Zhang, H Chuck; Kuo, Calvin J // Nature Medicine;Nov2015, Vol. 21 Issue 11, p1249 

    The article offers information on personalization of pancreatic cancer organoids using human pluripotent stem cells (hPSCs). Topics discussed include application of pharmacologic inhibition to restrict transforming growth factor (TGF) and notch signaling, testing of drug sensitivity and...

  • Involvement of TGFβ-Induced Phosphorylation of the PTEN C-Terminus on TGFβ-Induced Acquisition of Malignant Phenotypes in Lung Cancer Cells. Aoyama, Daisuke; Hashimoto, Naozumi; Sakamoto, Koji; Kohnoh, Takashi; Kusunose, Masaaki; Kimura, Motohiro; Ogata, Ryo; Imaizumi, Kazuyoshi; Kawabe, Tsutomu; Hasegawa, Yoshinori // PLoS ONE;Nov2013, Vol. 8 Issue 11, p1 

    Transforming growth factor β (TGFβ) derived from the tumor microenvironment induces malignant phenotypes such as epithelial-mesenchymal transition (EMT) and aberrant cell motility in lung cancers. TGFβ-induced translocation of β-catenin from E-cadherin complexes into the cytoplasm is...

  • Comparison of IGH Profile Signals Using t(4;14) and IGH Break-Apart Probes by FISH in Multiple Myeloma. Smol, Thomas; Daudignon, Agnès // Cytogenetic & Genome Research;Jan2018, Vol. 153 Issue 1, p18 

    We compared immunoglobulin heavy chain gene (IGH) signal patterns in multiple myeloma (MM) using the FGFR3-IGH and the IGH break-apart probes to facilitate their understanding and analysis. Forty-nine patients with MM were studied. FISH was performed on samples sorted with an FGFR3-IGH...

  • Smad4 induces the tumor suppressor E-cadherin and P-cadherin in colon carcinoma cells. Muller, Nicole; Reinacher-Schick, Anke; Baldus, Stephan; van Hengel, Jolanda; Berx, Geert; Baar, Anke; van Roy, Frans; Schmiegel, Wolff; Schwarte-Waldhoff, Irmgard // Oncogene;9/5/2002, Vol. 21 Issue 39, p6049 

    Provides information on a study which investigated the role of Smad4, an intracellular transmitter of transforming growth factor-β signals, in inducing classical cadherins indlucing the invasion of suppressor E-cadherin. Function of Smad4 in colon carcinoma cells; Results and discussion;...

  • Truncation of the TGF-β type II receptor gene results in insensitivity to TGF-β in human gastric cancer cells. Yang, Han-Kwang; Kang, Shin Hyeok; Kim, Yong-Seok; Won, Kyungshick; Bang, Yung-Jue; Kim, Seong-Jin // Oncogene;4/1/99, Vol. 18 Issue 13, p2213 

    The transforming growth factor-β (TGF-β receptor system has been implicated in the development of resistance to the growth-inhibitory effects of TGF-β. It has been reported that resistance to TGF-β correlates with inactivation of the TGF-β type II receptor (RII). In the present...

  • Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain. Ross, Jason P.; Lockett, Linda J.; Tabor, Bruce; Saunders, Ian W.; Young, Graeme P.; Macrae, Finlay; Blanco, Ignacio; Capella, Gabriel; Brown, Glenn S.; Lockett, Trevor J.; Hannan, Garry N. // BMC Cancer;2014, Vol. 14 Issue 1, p1 

    Background Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor β receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant...

  • The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway. Schmitt-Ney, Michel; Camussi, Giovanni // PLoS ONE;Mar2015, Vol. 10 Issue 3, p1 

    PAX3-FOXO1 (PAX3-FKHR) is the fusion protein produced by the genomic translocation that characterizes the alveolar subtype of Rhabdomyosarcoma, a pediatric sarcoma with myogenic phenotype. PAX3-FOXO1 is an aberrant but functional transcription factor. It retains PAX3-DNA-binding activity and...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics