Research Papers:

Overexpressing TPTE2 (TPIP), a homolog of the human tumor suppressor gene PTEN, rescues the abnormal phenotype of the PTEN–/– mutant

Daniel F. Lusche, Emma C. Buchele, Kanoe B. Russell, Benjamin A. Soll, Michele I. Vitolo, Michael R. Klemme, Deborah J. Wessels and David R. Soll _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:21100-21121. https://doi.org/10.18632/oncotarget.24941

Metrics: PDF 505 views  |   HTML 992 views  |   ?  


Daniel F. Lusche1, Emma C. Buchele1, Kanoe B. Russell1, Benjamin A. Soll1, Michele I.Vitolo2, Michael R. Klemme1, Deborah J. Wessels1 and David R. Soll1

1Developmental Studies Hybridoma Bank and W.M. Keck Dynamic Image Analysis Facility, Department of Biology, The University of Iowa, Iowa City, 52242 IA, USA

2Greenebaum Cancer Center, The University of Maryland, Baltimore, Maryland, Baltimore, 21201 MD, USA

Correspondence to:

David R. Soll, email: david-soll@uiowa.edu

Keywords: cancer cell rescue; tumor suppressor; transmembrane phosphatase; TPTE2 TPIP; wound healing

Received: November 16, 2017     Accepted: March 06, 2018     Published: April 20, 2018


One possible approach to normalize mutant cells that are metastatic and tumorigenic, is to upregulate a functionally similar homolog of the mutated gene. Here we have explored this hypothesis by generating an overexpressor of TPTE2 (TPIP), a homolog of PTEN, in PTEN–/– mutants, the latter generated by targeted mutagenesis of a human epithelial cell line. Overexpression of TPTE2 normalized phenotypic changes associated with the PTEN mutation. The PTEN–/–-associated changes rescued by overexpressing TPTE2 included 1) accelerated wound healing in the presence or absence of added growth factors (GFs), 2) increased division rates on a 2D substrate in the presence of GFs, 3) adhesion and viability on a 2D substrate in the absence of GFs, 4) viability in a 3D Matrigel model in the absence of GFs and substrate adhesion 5) loss of apoptosis-associated annexin V cell surface binding sites. The results justify further exploration into the possibility that upregulating TPTE2 by a drug may reverse metastatic and tumorigenic phenotypes mediated in part by a mutation in PTEN. This strategy may also be applicable to other tumorigenic mutations in which a homolog to the mutated gene is present and can substitute functionally.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 24941