Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay

Cancer Res. 1992 Feb 15;52(4):843-50.

Abstract

Distinct proteins complexed with somatostatin and the somatostatin analogue BIM-23014C were revealed in human breast cancer cells using the cross-linking assay. One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer, nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM-23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr 27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was visible in HBL-100. No correlation was found between receptors for BIM-23014C and epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr 27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000), two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and one had just the Mr 42,000 complex. The presence of the three BIM-23014C receptors was positively correlated (P less than 0.05) to the low amount of sex steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor negative, progesterone receptor negative) versus four of 14 (estrogen receptor positive, progesterone receptor positive)]. Another positive correlation was established between the absence of progesterone receptors and the presence of these three complexes [12 of 16 (progesterone receptor negative) versus four of 14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor-positive biopsies and its inhibitory activity would support its clinical potential for the treatment of breast cancer.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / metabolism*
  • Biopsy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Cell Line
  • ErbB Receptors / isolation & purification
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Middle Aged
  • Molecular Weight
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Oligopeptides / metabolism*
  • Oligopeptides / pharmacology
  • Peptides, Cyclic
  • Receptors, Estrogen / analysis
  • Receptors, Neurotransmitter / isolation & purification
  • Receptors, Neurotransmitter / metabolism*
  • Receptors, Progesterone / analysis
  • Receptors, Somatostatin
  • Somatostatin / analogs & derivatives*
  • Somatostatin / metabolism*
  • Somatostatin / pharmacology
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • Peptides, Cyclic
  • Receptors, Estrogen
  • Receptors, Neurotransmitter
  • Receptors, Progesterone
  • Receptors, Somatostatin
  • lanreotide
  • Somatostatin
  • ErbB Receptors