The uterine epithelial loss of Pten is inefficient to induce endometrial cancer with intact stromal Pten

PLoS Genetics
Xiaohuan LiangSudhansu K Dey

Abstract

Mutation of the tumor suppressor Pten often leads to tumorigenesis in various organs including the uterus. We previously showed that Pten deletion in the mouse uterus using a Pgr-Cre driver (Ptenf/fPgrCre/+) results in rapid development of endometrial carcinoma (EMC) with full penetration. We also reported that Pten deletion in the stroma and myometrium using Amhr2-Cre failed to initiate EMC. Since the Ptenf/fPgrCre/+ uterine epithelium was primarily affected by tumorigenesis despite its loss in both the epithelium and stroma, we wanted to know if Pten deletion in epithelia alone will induce tumorigenesis. We found that mice with uterine epithelial loss of Pten under a Ltf-iCre driver (Ptenf/f/LtfCre/+) develop uterine complex atypical hyperplasia (CAH), but rarely EMC even at 6 months of age. We observed that Ptenf/fPgrCre/+ uteri exhibit a unique population of cytokeratin 5 (CK5) and transformation related protein 63 (p63)-positive epithelial cells; these cells mark stratified epithelia and squamous differentiation. In contrast, Ptenf/fLtfCre/+ hyperplastic epithelia do not undergo stratification, but extensive epithelial cell apoptosis. This increased apoptosis is associated with elevation of TGFβ levels and activation of do...Continue Reading

References

Oct 1, 1988·Trends in Genetics : TIG·E Fuchs
Sep 15, 1995·Genes & Development·J P LydonB W O'Malley
Nov 5, 1997·Nature Genetics·D KongA Horii
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P MyersN K Tonks
Apr 11, 2000·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·S G Silverberg
Oct 15, 2003·Nature Reviews. Cancer·Peter M Siegel, Joan Massagué
Jan 20, 2004·Genes & Development·Maranke I KosterDennis R Roop
May 1, 2004·Molecular Endocrinology·Pancharatnam JeyasuriaKeith L Parker
Sep 10, 2005·International Journal of Cancer. Journal International Du Cancer·Ingunn M StefanssonLars A Akslen
Feb 14, 2006·Cell Research·He LiJun-Ping Liu
Mar 29, 2006·The Journal of Cell Biology·Jonathan M LeeErik W Thompson
Jun 30, 2007·Cancer·Sofia AsioliGianni Bussolati
Nov 28, 2007·Annual Review of Pathology·Antonio Di Cristofano, Lora Hedrick Ellenson
Jun 3, 2009·The Journal of Clinical Investigation·Raghu Kalluri, Robert A Weinberg
Jul 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jason R RockBrigid L M Hogan
Sep 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sanaz MemarzadehOwen N Witte
Mar 15, 2011·Experimental Cell Research·Ayesha Joshi, Lora Hedrick Ellenson
May 17, 2011·Gynecologic Oncology·Takiko DaikokuSudhansu K Dey
Jun 28, 2011·Cell·Karine Lefort, G Paolo Dotto
Sep 28, 2012·The International Journal of Biological Markers·Hong-Qiang GuoShu-Jun Yang
May 16, 2014·Endocrinology·Takiko DaikokuSudhansu K Dey
May 30, 2014·The Lancet Oncology·Rajmohan MuraliBritta Weigelt
Jun 24, 2014·Women's Health·Pratibha S Binder, David G Mutch
Jul 25, 2014·The American Journal of Pathology·Takiko DaikokuSudhansu K Dey
Oct 9, 2014·Frontiers in Oncology·Amancio Carnero, Jesus M Paramio
Feb 24, 2015·The American Journal of Pathology·Ayesha JoshiLora H Ellenson
Jul 19, 2017·Trends in Cancer·Selcuk Colak, Peter Ten Dijke

❮ Previous
Next ❯

Citations

Feb 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jumpei TerakawaTakeshi Kurita
Aug 21, 2019·Cold Spring Harbor Perspectives in Medicine·Katie A ThiesMichael C Ostrowski
May 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Diana MonsivaisMartin M Matzuk
Nov 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ileana C CuevasDiego H Castrillon
Feb 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Qinglei Li
Jul 13, 2020·Cancer Science·Satoru KyoKentaro Nakayama
Nov 9, 2020·European Journal of Pharmacology·Runali SankheAnoop Kishore

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
RNAseq
Genotyping

Software Mentioned

ImageJ

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.