Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma

Michael H. Muders, Shamit K. Dutta, Ling Wang, Julie S. Lau, Resham Bhattacharya, Thomas C. Smyrk, Suresh T. Chari, Kaustubh Datta, Debabrata Mukhopadhyay

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Abstract

Regulator of G-protein signaling-GAIP-interacting protein COOH terminus (GIPC) is involved in protein trafficking, endocytosis, and receptor clustering and is associated with insulin-like growth factor I receptor (IGF-IR), a receptor important for proliferation and anchorage-independent growth. Here, we described GIPC expression in different human pancreatic adenocarcinoma (PCA) cell lines and we examined the role of GIPC in the regulation of IGF-IR protein levels in PCA. Interestingly, inhibition of GIPC expression by RNA interference led to reduced IGF-IR protein levels and a subsequent decrease in proliferation of PCA cells. We also determined that the PDZ domain of GIPC is essential for the post-translational regulation and the binding of IGF-IR. The importance of GIPC in pancreatic cancer development and progression is supported by tissue microarray data of 300 pancreatic cancer specimens where GIPC is highly expressed in PCA. Taken together, our data suggest that GIPC is a central molecule for the stability of IGF-IR and could be a target for future therapy.

Original languageEnglish (US)
Pages (from-to)10264-10268
Number of pages5
JournalCancer Research
Volume66
Issue number21
DOIs
StatePublished - Nov 1 2006

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Adenocarcinoma
IGF Type 1 Receptor
Proteins
Pancreatic Neoplasms
GTP-Binding Protein Regulators
PDZ Domains
Protein Transport
RNA Interference
Endocytosis
Cluster Analysis
Cell Line
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Muders, M. H., Dutta, S. K., Wang, L., Lau, J. S., Bhattacharya, R., Smyrk, T. C., ... Mukhopadhyay, D. (2006). Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma. Cancer Research, 66(21), 10264-10268. https://doi.org/10.1158/0008-5472.CAN-06-2321

Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma. / Muders, Michael H.; Dutta, Shamit K.; Wang, Ling; Lau, Julie S.; Bhattacharya, Resham; Smyrk, Thomas C.; Chari, Suresh T.; Datta, Kaustubh; Mukhopadhyay, Debabrata.

In: Cancer Research, Vol. 66, No. 21, 01.11.2006, p. 10264-10268.

Research output: Contribution to journalArticle

Muders, MH, Dutta, SK, Wang, L, Lau, JS, Bhattacharya, R, Smyrk, TC, Chari, ST, Datta, K & Mukhopadhyay, D 2006, 'Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma', Cancer Research, vol. 66, no. 21, pp. 10264-10268. https://doi.org/10.1158/0008-5472.CAN-06-2321
Muders MH, Dutta SK, Wang L, Lau JS, Bhattacharya R, Smyrk TC et al. Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma. Cancer Research. 2006 Nov 1;66(21):10264-10268. https://doi.org/10.1158/0008-5472.CAN-06-2321
Muders, Michael H. ; Dutta, Shamit K. ; Wang, Ling ; Lau, Julie S. ; Bhattacharya, Resham ; Smyrk, Thomas C. ; Chari, Suresh T. ; Datta, Kaustubh ; Mukhopadhyay, Debabrata. / Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma. In: Cancer Research. 2006 ; Vol. 66, No. 21. pp. 10264-10268.
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