Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity

Hae Seong Yoon, Terrence Monks, Jeffrey I. Everitt, Cheryl L. Walker, Serrine Lau

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Although 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ; 2.5 μmol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type (Tsc2+/+) and mutant Eker rats (Tsc2EK/+), only TGHQ-treated Tsc2EK/+ rats developed renal tumors, indicating that cell proliferation per se was not sufficient for tumor development. Tuberin expression was initially induced within the OSOM after TGHQ treatment but was lost within TGHQ-induced renal tumors. High extracellular signal-regulated kinase (ERK) activity occurred in the OSOM of Tsc2EK/+ rats at 4 mo and in TGHQ-induced renal tumors. Cyclin D1 was also highly expressed in TGHQ-induced renal tumors. Reexpression of Tsc2 in tuberin-negative cells decreased ERK activity, consistent with the growth-suppressive effects of this tumor suppressor gene. Thus 1) stimulation of cell proliferation after toxicant insult is insufficient for tumor formation; 2) tuberin induction after acute tissue injury suggests that Tsc2 is an acute-phase response gene, limiting the proliferative response after injury; and 3) loss of Tsc2 gene function is associated with cell cycle deregulation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number2 52-2
StatePublished - 2002
Externally publishedYes

Fingerprint

Cell Proliferation
Kidney
Neoplasms
Extracellular Signal-Regulated MAP Kinases
Kidney Medulla
Acute-Phase Reaction
Cyclin D1
Wounds and Injuries
Tumor Suppressor Genes
Genes
tuberous sclerosis complex 2 protein
Cell Cycle
Growth

Keywords

  • Carcinogenesis
  • Cell cycle
  • Kidney
  • Tsc2 gene

ASJC Scopus subject areas

  • Physiology

Cite this

Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity. / Yoon, Hae Seong; Monks, Terrence; Everitt, Jeffrey I.; Walker, Cheryl L.; Lau, Serrine.

In: American Journal of Physiology - Renal Physiology, Vol. 283, No. 2 52-2, 2002.

Research output: Contribution to journalArticle

@article{405eb7a6e5b64e9f9303938c169a67aa,
title = "Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity",
abstract = "Although 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ; 2.5 μmol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type (Tsc2+/+) and mutant Eker rats (Tsc2EK/+), only TGHQ-treated Tsc2EK/+ rats developed renal tumors, indicating that cell proliferation per se was not sufficient for tumor development. Tuberin expression was initially induced within the OSOM after TGHQ treatment but was lost within TGHQ-induced renal tumors. High extracellular signal-regulated kinase (ERK) activity occurred in the OSOM of Tsc2EK/+ rats at 4 mo and in TGHQ-induced renal tumors. Cyclin D1 was also highly expressed in TGHQ-induced renal tumors. Reexpression of Tsc2 in tuberin-negative cells decreased ERK activity, consistent with the growth-suppressive effects of this tumor suppressor gene. Thus 1) stimulation of cell proliferation after toxicant insult is insufficient for tumor formation; 2) tuberin induction after acute tissue injury suggests that Tsc2 is an acute-phase response gene, limiting the proliferative response after injury; and 3) loss of Tsc2 gene function is associated with cell cycle deregulation.",
keywords = "Carcinogenesis, Cell cycle, Kidney, Tsc2 gene",
author = "Yoon, {Hae Seong} and Terrence Monks and Everitt, {Jeffrey I.} and Walker, {Cheryl L.} and Serrine Lau",
year = "2002",
language = "English (US)",
volume = "283",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "2 52-2",

}

TY - JOUR

T1 - Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity

AU - Yoon, Hae Seong

AU - Monks, Terrence

AU - Everitt, Jeffrey I.

AU - Walker, Cheryl L.

AU - Lau, Serrine

PY - 2002

Y1 - 2002

N2 - Although 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ; 2.5 μmol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type (Tsc2+/+) and mutant Eker rats (Tsc2EK/+), only TGHQ-treated Tsc2EK/+ rats developed renal tumors, indicating that cell proliferation per se was not sufficient for tumor development. Tuberin expression was initially induced within the OSOM after TGHQ treatment but was lost within TGHQ-induced renal tumors. High extracellular signal-regulated kinase (ERK) activity occurred in the OSOM of Tsc2EK/+ rats at 4 mo and in TGHQ-induced renal tumors. Cyclin D1 was also highly expressed in TGHQ-induced renal tumors. Reexpression of Tsc2 in tuberin-negative cells decreased ERK activity, consistent with the growth-suppressive effects of this tumor suppressor gene. Thus 1) stimulation of cell proliferation after toxicant insult is insufficient for tumor formation; 2) tuberin induction after acute tissue injury suggests that Tsc2 is an acute-phase response gene, limiting the proliferative response after injury; and 3) loss of Tsc2 gene function is associated with cell cycle deregulation.

AB - Although 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ; 2.5 μmol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type (Tsc2+/+) and mutant Eker rats (Tsc2EK/+), only TGHQ-treated Tsc2EK/+ rats developed renal tumors, indicating that cell proliferation per se was not sufficient for tumor development. Tuberin expression was initially induced within the OSOM after TGHQ treatment but was lost within TGHQ-induced renal tumors. High extracellular signal-regulated kinase (ERK) activity occurred in the OSOM of Tsc2EK/+ rats at 4 mo and in TGHQ-induced renal tumors. Cyclin D1 was also highly expressed in TGHQ-induced renal tumors. Reexpression of Tsc2 in tuberin-negative cells decreased ERK activity, consistent with the growth-suppressive effects of this tumor suppressor gene. Thus 1) stimulation of cell proliferation after toxicant insult is insufficient for tumor formation; 2) tuberin induction after acute tissue injury suggests that Tsc2 is an acute-phase response gene, limiting the proliferative response after injury; and 3) loss of Tsc2 gene function is associated with cell cycle deregulation.

KW - Carcinogenesis

KW - Cell cycle

KW - Kidney

KW - Tsc2 gene

UR - http://www.scopus.com/inward/record.url?scp=0036068587&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036068587&partnerID=8YFLogxK

M3 - Article

C2 - 12110509

AN - SCOPUS:0036068587

VL - 283

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 2 52-2

ER -