Expression of specificity protein transcription factors in pancreatic cancer and their association in prognosis and therapy

Umesh Tanaji Sankpal, Pius Maliakal, Debashish Bose, Omar Kayaleh, Daniel Buchholz, Riyaz Mahammad Basha

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Pancreatic cancer is an aggressive malignancy with poor prognosis. Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Due to the aggressive nature of this malignancy, there is a serious concern for identifying effective targets, and adopting novel strategies for therapy. Members of the Specificity Protein (Sp) family of transcription factors, Sp1, Sp3, and Sp4 regulate the expression of a number of genes associated with cancer cell proliferation, differentiation, and metastasis. Sp1 levels are upregulated in pancreatic cancer cell lines, and surgically resected human pancreatic adenocarcinoma. Sp1 overexpression in tumor tissues is associated with aggressive disease, poor prognosis and inversely correlated with survival. Sp1 is also known to affect angiogenesis by regulating the expression of vascular endothelial growth factor and its receptors. Results from clinical studies suggest Sp1 as new biomarker to identify aggressive pancreatic ductal adenocarcinoma. The pharmacological inhibition of Sp1 using agents such as celecoxib, mithramycin, curcumin, and tolfenamic acid has showed promising results in pre-clinical studies and demonstrated Sp transcription factors as potential targets for pancreatic cancer therapy. This review summarizes studies showing the association of Sp proteins with this malignancy, with a special emphasis on pre-clinical studies that tested strategies to target Sp transcription factors for inhibiting human pancreatic cancer cell proliferation and tumor growth in laboratory animals. The results showed remarkable efficacy and suggest that such approaches have the potential for high success in developing clinically relevant strategies for treating pancreatic cancer.

Original languageEnglish
Pages (from-to)3779-3786
Number of pages8
JournalCurrent Medicinal Chemistry
Volume19
Issue number22
DOIs
StatePublished - 1 Aug 2012

Fingerprint

Sp Transcription Factors
Pancreatic Neoplasms
Celecoxib
Cell proliferation
Association reactions
Tumors
Plicamycin
Sp1 Transcription Factor
Neoplasms
Vascular Endothelial Growth Factor Receptor
Proteins
Curcumin
Biomarkers
Adenocarcinoma
Animals
Therapeutics
Genes
Cells
Tissue
Cell Proliferation

Keywords

  • Mucins
  • Pancreatic cancer
  • Sp1
  • Survivin
  • Transcription factors

Cite this

@article{c1ec036302484deebddbcb8e4d34f9f9,
title = "Expression of specificity protein transcription factors in pancreatic cancer and their association in prognosis and therapy",
abstract = "Pancreatic cancer is an aggressive malignancy with poor prognosis. Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Due to the aggressive nature of this malignancy, there is a serious concern for identifying effective targets, and adopting novel strategies for therapy. Members of the Specificity Protein (Sp) family of transcription factors, Sp1, Sp3, and Sp4 regulate the expression of a number of genes associated with cancer cell proliferation, differentiation, and metastasis. Sp1 levels are upregulated in pancreatic cancer cell lines, and surgically resected human pancreatic adenocarcinoma. Sp1 overexpression in tumor tissues is associated with aggressive disease, poor prognosis and inversely correlated with survival. Sp1 is also known to affect angiogenesis by regulating the expression of vascular endothelial growth factor and its receptors. Results from clinical studies suggest Sp1 as new biomarker to identify aggressive pancreatic ductal adenocarcinoma. The pharmacological inhibition of Sp1 using agents such as celecoxib, mithramycin, curcumin, and tolfenamic acid has showed promising results in pre-clinical studies and demonstrated Sp transcription factors as potential targets for pancreatic cancer therapy. This review summarizes studies showing the association of Sp proteins with this malignancy, with a special emphasis on pre-clinical studies that tested strategies to target Sp transcription factors for inhibiting human pancreatic cancer cell proliferation and tumor growth in laboratory animals. The results showed remarkable efficacy and suggest that such approaches have the potential for high success in developing clinically relevant strategies for treating pancreatic cancer.",
keywords = "Mucins, Pancreatic cancer, Sp1, Survivin, Transcription factors",
author = "Sankpal, {Umesh Tanaji} and Pius Maliakal and Debashish Bose and Omar Kayaleh and Daniel Buchholz and Basha, {Riyaz Mahammad}",
year = "2012",
month = "8",
day = "1",
doi = "10.2174/092986712801661077",
language = "English",
volume = "19",
pages = "3779--3786",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "22",

}

Expression of specificity protein transcription factors in pancreatic cancer and their association in prognosis and therapy. / Sankpal, Umesh Tanaji; Maliakal, Pius; Bose, Debashish; Kayaleh, Omar; Buchholz, Daniel; Basha, Riyaz Mahammad.

In: Current Medicinal Chemistry, Vol. 19, No. 22, 01.08.2012, p. 3779-3786.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Expression of specificity protein transcription factors in pancreatic cancer and their association in prognosis and therapy

AU - Sankpal, Umesh Tanaji

AU - Maliakal, Pius

AU - Bose, Debashish

AU - Kayaleh, Omar

AU - Buchholz, Daniel

AU - Basha, Riyaz Mahammad

PY - 2012/8/1

Y1 - 2012/8/1

N2 - Pancreatic cancer is an aggressive malignancy with poor prognosis. Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Due to the aggressive nature of this malignancy, there is a serious concern for identifying effective targets, and adopting novel strategies for therapy. Members of the Specificity Protein (Sp) family of transcription factors, Sp1, Sp3, and Sp4 regulate the expression of a number of genes associated with cancer cell proliferation, differentiation, and metastasis. Sp1 levels are upregulated in pancreatic cancer cell lines, and surgically resected human pancreatic adenocarcinoma. Sp1 overexpression in tumor tissues is associated with aggressive disease, poor prognosis and inversely correlated with survival. Sp1 is also known to affect angiogenesis by regulating the expression of vascular endothelial growth factor and its receptors. Results from clinical studies suggest Sp1 as new biomarker to identify aggressive pancreatic ductal adenocarcinoma. The pharmacological inhibition of Sp1 using agents such as celecoxib, mithramycin, curcumin, and tolfenamic acid has showed promising results in pre-clinical studies and demonstrated Sp transcription factors as potential targets for pancreatic cancer therapy. This review summarizes studies showing the association of Sp proteins with this malignancy, with a special emphasis on pre-clinical studies that tested strategies to target Sp transcription factors for inhibiting human pancreatic cancer cell proliferation and tumor growth in laboratory animals. The results showed remarkable efficacy and suggest that such approaches have the potential for high success in developing clinically relevant strategies for treating pancreatic cancer.

AB - Pancreatic cancer is an aggressive malignancy with poor prognosis. Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in the United States. Due to the aggressive nature of this malignancy, there is a serious concern for identifying effective targets, and adopting novel strategies for therapy. Members of the Specificity Protein (Sp) family of transcription factors, Sp1, Sp3, and Sp4 regulate the expression of a number of genes associated with cancer cell proliferation, differentiation, and metastasis. Sp1 levels are upregulated in pancreatic cancer cell lines, and surgically resected human pancreatic adenocarcinoma. Sp1 overexpression in tumor tissues is associated with aggressive disease, poor prognosis and inversely correlated with survival. Sp1 is also known to affect angiogenesis by regulating the expression of vascular endothelial growth factor and its receptors. Results from clinical studies suggest Sp1 as new biomarker to identify aggressive pancreatic ductal adenocarcinoma. The pharmacological inhibition of Sp1 using agents such as celecoxib, mithramycin, curcumin, and tolfenamic acid has showed promising results in pre-clinical studies and demonstrated Sp transcription factors as potential targets for pancreatic cancer therapy. This review summarizes studies showing the association of Sp proteins with this malignancy, with a special emphasis on pre-clinical studies that tested strategies to target Sp transcription factors for inhibiting human pancreatic cancer cell proliferation and tumor growth in laboratory animals. The results showed remarkable efficacy and suggest that such approaches have the potential for high success in developing clinically relevant strategies for treating pancreatic cancer.

KW - Mucins

KW - Pancreatic cancer

KW - Sp1

KW - Survivin

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=84865210270&partnerID=8YFLogxK

U2 - 10.2174/092986712801661077

DO - 10.2174/092986712801661077

M3 - Review article

C2 - 22725697

AN - SCOPUS:84865210270

VL - 19

SP - 3779

EP - 3786

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 22

ER -