Activation of Grm1 expression by mutated BRaf (V600E) in vitro and in vivo

Oncotarget
Ho-Chung ChenSuzie Chen

Abstract

Our laboratory previously showed that ectopic expression of Grm1 is sufficient to induce spontaneous melanoma formation with 100% penetrance in transgenic mouse model, TG-3, which harbors wild-type BRaf. Studies identified Grm1 expression in human melanoma cell lines and primary to secondary metastatic melanoma biopsies having wild-type or mutated BRaf, but not in normal melanocytes or benign nevi. Grm1 expression was detected in tissues from mice genetically engineered with inducible melanocyte-specific BRafV600E. Additionally, stable clones derived from introduction of exogenous BRafV600E in mouse melanocytes also showed Grm1 expression, which was not detected in the parental or empty vector-derived cells, suggesting that expression of BRafV600E could activate Grm1 expression. Despite aberrant Grm1 expression in the inducible, melanocyte-specific BRafV600E mice, no tumors formed. However, in older mice, the melanocytes underwent senescence, as demonstrated previously by others. It was proposed that upregulated p15 and TGFβ contributed to the senescence phenotype. In contrast, in older TG-3 mice the levels of p15 and TGFβ remained the same or lower. Taken together, these results suggest the temporal regulation on the expressio...Continue Reading

References

May 1, 1996·The Journal of Investigative Dermatology·S ChenM A Philbert
May 20, 2000·Advances in Cancer Research·N BardeesyL Chin
Mar 21, 2002·Journal of the National Cancer Institute·Elena V SviderskayaDorothy C Bennett
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Nov 26, 2002·Nature Genetics·Pamela M PollockPaul S Meltzer
May 6, 2006·Genesis : the Journal of Genetics and Development·Marcus BosenbergLynda Chin
Aug 2, 2006·Methods in Molecular Biology·Kanchana Natarajan, Bradford C Berk
Jan 9, 2007·Current Opinion in Genetics & Development·Nathalie Dhomen, Richard Marais
Mar 3, 2007·Cancer Research·Jin NamkoongSuzie Chen
Nov 16, 2007·Trends in Pharmacological Sciences·Nicolas DelcourtPhilippe Marin
Jan 15, 2008·Oncogene·S Courtois-CoxK Cichowski
Apr 26, 2008·Pigment Cell & Melanoma Research·Seung-Shick ShinSuzie Chen
Mar 14, 2009·Nature Genetics·David DankortMarcus Bosenberg
Apr 7, 2009·Cancer Cell·Nathalie DhomenRichard Marais
Jun 16, 2009·Histochemistry and Cell Biology·Andrzej StepulakChrysanthy Ikonomidou
Sep 4, 2009·Nature·Thanashan RajakulendranMarc Therrien
Oct 22, 2009·Pigment Cell & Melanoma Research·Seung-Shick ShinSuzie Chen
Jan 22, 2011·Cancer Cell·Poulikos I Poulikakos, Neal Rosen
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Jan 21, 2012·Biochemical Society Transactions·Edita AksamitieneBoris N Kholodenko
Feb 24, 2012·The New England Journal of Medicine·Jeffrey A SosmanAntoni Ribas
Apr 6, 2012·Nature Reviews. Cancer·Keith T FlahertyDavid E Fisher
Jun 1, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Todd D Prickett, Yardena Samuels
Jun 5, 2012·Genes & Development·Hensin TsaoDavid E Fisher
Jul 17, 2012·Molecular Cancer Research : MCR·Janet Wangari-TalbotSuzie Chen
Jan 29, 2013·Molecular Cell·Alyson K FreemanDeborah K Morrison
Apr 16, 2013·Cancer Metastasis Reviews·Yabin ChengGang Li
Jun 26, 2013·Chemistry & Biology·Daniel K Treiber, Neil P Shah
Aug 29, 2013·International Journal of Biological Sciences·Stacey S Willard, Shahriar Koochekpour
Aug 30, 2013·Small GTPases·Alyson K FreemanDeborah K Morrison
Sep 3, 2013·Cell·Jiancheng HuAndrey S Shaw
Oct 25, 2013·International Journal of Biological Sciences·Stacey S Willard, Shahriar Koochekpour
Sep 4, 2014·Cold Spring Harbor Perspectives in Medicine·Elena B Hawryluk, Hensin Tsao
Sep 16, 2014·Trends in Biochemical Sciences·Hugo LavoieFrank Sicheri
Apr 25, 2015·Nature Reviews. Molecular Cell Biology·Hugo Lavoie, Marc Therrien
Jul 18, 2015·Cancer Discovery·Andrew S McNealTodd W Ridky
Sep 1, 2015·Frontiers in Oncology·Giuseppe PalmieriAntonio Cossu
Jan 6, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

❮ Previous
Next ❯

Citations

Jun 7, 2019·Pigment Cell & Melanoma Research·Lena FeuererAnja Katrin Bosserhoff
Aug 8, 2021·Cancers·Kevinn Eddy, Suzie Chen

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
electrophoresis
transfections

Software Mentioned

Aperio ImageScope

Related Concepts

Related Feeds

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.