Pem renders tumor cells resistant to apoptotic cell death induced by a CD8+ T cell-mediated immune response or anticancer drug treatment

Seok Ho Kim, Keon Woo Kim, Jin Hee Kim, Kyung Hee Noh, Hyun Cheol Bae, Tae Hoon Lee, Tae Woo Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Pem, a member of homeobox genes, is an oncofetal gene which is preferentially expressed in reproductive tissues and in multiple tumor cell lines. However, the function of Pem in tumor cell lines has not been elucidated. Herein we report that the ectopic expression of Pem in TC-1, a human papillomavirus type 16 (HPV-16) E7-expressing surrogate cervical tumor cell line, demonstrated a significant increase in extracellular signal-regulated kinase (ERK) activity and multiple resistance to various apoptotic pressures from an E7-specific CD8+ T cell-mediated immune response and anticancer drug treatment. The observed resistance to apoptotic death of the Pem-over-expressing TC-1 tumor cells (TC-1/Pem) was associated with the down-regulation of a pro-apoptotic molecule, such as BIM, and up-regulation of an anti-apoptotic molecule, such as Bcl-2 protein, which mediated ERK activation. We also observed that the intratumoral injection of an ERK inhibitor enhanced the therapeutic efficacy of E7-specific CD8+ T cell adoptive transfer or anticancer drug treatment against the resistant TC-1/Pem tumor. This is the first evidence demonstrating an association between Pem and a signaling pathway, namely the ERK-mediated survival signal transduction pathway. Thus, our data indicate that activation of the ERK pathway represents a new mechanism of Pem-mediated multiple resistances and the present research will contribute to the development of a novel strategy in cancer therapy against Pem-over-expressing tumor cells.

Original languageEnglish
Pages (from-to)181-188
Number of pages8
JournalCancer Letters
Volume293
Issue number2
DOIs
Publication statusPublished - 2010 Jul 1

Fingerprint

Drug therapy
T-cells
Extracellular Signal-Regulated MAP Kinases
Cell death
Tumors
Cell Death
Cells
T-Lymphocytes
Tumor Cell Line
Pharmaceutical Preparations
Neoplasms
Therapeutics
Genes
Chemical activation
Human papillomavirus 16
Adoptive Transfer
Homeobox Genes
Signal transduction
Molecules
Signal Transduction

Keywords

  • Chemotherapy
  • Cytotoxic T lymphocyte
  • ERK pathway
  • Immune resistance
  • Pem

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pem renders tumor cells resistant to apoptotic cell death induced by a CD8+ T cell-mediated immune response or anticancer drug treatment. / Kim, Seok Ho; Kim, Keon Woo; Kim, Jin Hee; Noh, Kyung Hee; Bae, Hyun Cheol; Lee, Tae Hoon; Kim, Tae Woo.

In: Cancer Letters, Vol. 293, No. 2, 01.07.2010, p. 181-188.

Research output: Contribution to journalArticle

Kim, Seok Ho ; Kim, Keon Woo ; Kim, Jin Hee ; Noh, Kyung Hee ; Bae, Hyun Cheol ; Lee, Tae Hoon ; Kim, Tae Woo. / Pem renders tumor cells resistant to apoptotic cell death induced by a CD8+ T cell-mediated immune response or anticancer drug treatment. In: Cancer Letters. 2010 ; Vol. 293, No. 2. pp. 181-188.
@article{3c61886b613044ba84913596554f33dd,
title = "Pem renders tumor cells resistant to apoptotic cell death induced by a CD8+ T cell-mediated immune response or anticancer drug treatment",
abstract = "Pem, a member of homeobox genes, is an oncofetal gene which is preferentially expressed in reproductive tissues and in multiple tumor cell lines. However, the function of Pem in tumor cell lines has not been elucidated. Herein we report that the ectopic expression of Pem in TC-1, a human papillomavirus type 16 (HPV-16) E7-expressing surrogate cervical tumor cell line, demonstrated a significant increase in extracellular signal-regulated kinase (ERK) activity and multiple resistance to various apoptotic pressures from an E7-specific CD8+ T cell-mediated immune response and anticancer drug treatment. The observed resistance to apoptotic death of the Pem-over-expressing TC-1 tumor cells (TC-1/Pem) was associated with the down-regulation of a pro-apoptotic molecule, such as BIM, and up-regulation of an anti-apoptotic molecule, such as Bcl-2 protein, which mediated ERK activation. We also observed that the intratumoral injection of an ERK inhibitor enhanced the therapeutic efficacy of E7-specific CD8+ T cell adoptive transfer or anticancer drug treatment against the resistant TC-1/Pem tumor. This is the first evidence demonstrating an association between Pem and a signaling pathway, namely the ERK-mediated survival signal transduction pathway. Thus, our data indicate that activation of the ERK pathway represents a new mechanism of Pem-mediated multiple resistances and the present research will contribute to the development of a novel strategy in cancer therapy against Pem-over-expressing tumor cells.",
keywords = "Chemotherapy, Cytotoxic T lymphocyte, ERK pathway, Immune resistance, Pem",
author = "Kim, {Seok Ho} and Kim, {Keon Woo} and Kim, {Jin Hee} and Noh, {Kyung Hee} and Bae, {Hyun Cheol} and Lee, {Tae Hoon} and Kim, {Tae Woo}",
year = "2010",
month = "7",
day = "1",
doi = "10.1016/j.canlet.2010.01.008",
language = "English",
volume = "293",
pages = "181--188",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "2",

}

TY - JOUR

T1 - Pem renders tumor cells resistant to apoptotic cell death induced by a CD8+ T cell-mediated immune response or anticancer drug treatment

AU - Kim, Seok Ho

AU - Kim, Keon Woo

AU - Kim, Jin Hee

AU - Noh, Kyung Hee

AU - Bae, Hyun Cheol

AU - Lee, Tae Hoon

AU - Kim, Tae Woo

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Pem, a member of homeobox genes, is an oncofetal gene which is preferentially expressed in reproductive tissues and in multiple tumor cell lines. However, the function of Pem in tumor cell lines has not been elucidated. Herein we report that the ectopic expression of Pem in TC-1, a human papillomavirus type 16 (HPV-16) E7-expressing surrogate cervical tumor cell line, demonstrated a significant increase in extracellular signal-regulated kinase (ERK) activity and multiple resistance to various apoptotic pressures from an E7-specific CD8+ T cell-mediated immune response and anticancer drug treatment. The observed resistance to apoptotic death of the Pem-over-expressing TC-1 tumor cells (TC-1/Pem) was associated with the down-regulation of a pro-apoptotic molecule, such as BIM, and up-regulation of an anti-apoptotic molecule, such as Bcl-2 protein, which mediated ERK activation. We also observed that the intratumoral injection of an ERK inhibitor enhanced the therapeutic efficacy of E7-specific CD8+ T cell adoptive transfer or anticancer drug treatment against the resistant TC-1/Pem tumor. This is the first evidence demonstrating an association between Pem and a signaling pathway, namely the ERK-mediated survival signal transduction pathway. Thus, our data indicate that activation of the ERK pathway represents a new mechanism of Pem-mediated multiple resistances and the present research will contribute to the development of a novel strategy in cancer therapy against Pem-over-expressing tumor cells.

AB - Pem, a member of homeobox genes, is an oncofetal gene which is preferentially expressed in reproductive tissues and in multiple tumor cell lines. However, the function of Pem in tumor cell lines has not been elucidated. Herein we report that the ectopic expression of Pem in TC-1, a human papillomavirus type 16 (HPV-16) E7-expressing surrogate cervical tumor cell line, demonstrated a significant increase in extracellular signal-regulated kinase (ERK) activity and multiple resistance to various apoptotic pressures from an E7-specific CD8+ T cell-mediated immune response and anticancer drug treatment. The observed resistance to apoptotic death of the Pem-over-expressing TC-1 tumor cells (TC-1/Pem) was associated with the down-regulation of a pro-apoptotic molecule, such as BIM, and up-regulation of an anti-apoptotic molecule, such as Bcl-2 protein, which mediated ERK activation. We also observed that the intratumoral injection of an ERK inhibitor enhanced the therapeutic efficacy of E7-specific CD8+ T cell adoptive transfer or anticancer drug treatment against the resistant TC-1/Pem tumor. This is the first evidence demonstrating an association between Pem and a signaling pathway, namely the ERK-mediated survival signal transduction pathway. Thus, our data indicate that activation of the ERK pathway represents a new mechanism of Pem-mediated multiple resistances and the present research will contribute to the development of a novel strategy in cancer therapy against Pem-over-expressing tumor cells.

KW - Chemotherapy

KW - Cytotoxic T lymphocyte

KW - ERK pathway

KW - Immune resistance

KW - Pem

UR - http://www.scopus.com/inward/record.url?scp=77952514777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952514777&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2010.01.008

DO - 10.1016/j.canlet.2010.01.008

M3 - Article

C2 - 20137854

AN - SCOPUS:77952514777

VL - 293

SP - 181

EP - 188

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 2

ER -