IQGAP1 in rectal adenocarcinomas: Localization and protein expression before and after radiochemotherapy

TY - JOUR

T1 - IQGAP1 in rectal adenocarcinomas

T2 - Localization and protein expression before and after radiochemotherapy

AU - Holck, Susanne

AU - Nielsen, Hans Jørgen

AU - Hammer, Emilie

AU - Christensen, Ib Jarle

AU - Larsson, Lars-Inge

N1 - Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

PY - 2015/1/28

Y1 - 2015/1/28

N2 - Treatment of rectal adenocarcinoma includes total mesorectal excision, which is preceded by radiochemotherapy (RCT) in cases of advanced disease. The response to RCT varies from total tumor regression to no effect but this heterogeneous response is unexplained. However, both radiation and treatment with 5-fluorouracil may induce treatment resistance through upregulation of the mitogen-activated protein kinase (MAPK) cascade. IQGAP1 is a scaffold protein that appears to be essential to MAPK signaling in cancers. We have therefore studied IQGAP1 protein expression in rectal adenocarcinomas before and after RCT. We demonstrate that cancer cells show increased apical staining for IQGAP1 following RCT. Interestingly, this increase is significantly higher in patients showing poor RCT responses. Our results also suggest that low levels of apical IQGAP1-staining in biopsies may predict the RCT response. Together, these data suggest that both the level and localization of IQGAP1 may influence the treatment response.

AB - Treatment of rectal adenocarcinoma includes total mesorectal excision, which is preceded by radiochemotherapy (RCT) in cases of advanced disease. The response to RCT varies from total tumor regression to no effect but this heterogeneous response is unexplained. However, both radiation and treatment with 5-fluorouracil may induce treatment resistance through upregulation of the mitogen-activated protein kinase (MAPK) cascade. IQGAP1 is a scaffold protein that appears to be essential to MAPK signaling in cancers. We have therefore studied IQGAP1 protein expression in rectal adenocarcinomas before and after RCT. We demonstrate that cancer cells show increased apical staining for IQGAP1 following RCT. Interestingly, this increase is significantly higher in patients showing poor RCT responses. Our results also suggest that low levels of apical IQGAP1-staining in biopsies may predict the RCT response. Together, these data suggest that both the level and localization of IQGAP1 may influence the treatment response.

KW - Adenocarcinoma

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antimetabolites, Antineoplastic

KW - Biomarkers, Tumor

KW - Capecitabine

KW - Chemoradiotherapy

KW - Deoxycytidine

KW - Female

KW - Fluorouracil

KW - Follow-Up Studies

KW - Humans

KW - Immunoenzyme Techniques

KW - Male

KW - Middle Aged

KW - Neoplasm Invasiveness

KW - Neoplasm Staging

KW - Prognosis

KW - Rectal Neoplasms

KW - Young Adult

KW - ras GTPase-Activating Proteins

U2 - 10.1016/j.canlet.2014.10.005

DO - 10.1016/j.canlet.2014.10.005

M3 - Journal article

C2 - 25305455

SN - 0304-3835

VL - 356

SP - 556

EP - 560

JO - Cancer Letters

JF - Cancer Letters

IS - 2 Pt B

ER -