Effects of epidermal growth factor and analogues of luteinizing hormone-releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors

Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1656-60. doi: 10.1073/pnas.88.5.1656.

Abstract

Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Autoradiography
  • Breast Neoplasms
  • Cell Line
  • Colonic Neoplasms
  • Epidermal Growth Factor / pharmacology*
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / pharmacology*
  • Humans
  • Kinetics
  • Lung Neoplasms
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Pancreatic Neoplasms
  • Phosphorus Radioisotopes
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology*
  • Triptorelin Pamoate
  • Tyrosine

Substances

  • Antineoplastic Agents
  • Membrane Proteins
  • Phosphorus Radioisotopes
  • Triptorelin Pamoate
  • vapreotide
  • Gonadotropin-Releasing Hormone
  • Tyrosine
  • Somatostatin
  • Epidermal Growth Factor
  • Protein Kinases
  • Protein-Tyrosine Kinases