Expression of Luteinizing Hormone-Releasing Hormone (LHRH) and Type-I LHRH Receptor in Transitional Cell Carcinoma Type of Human Bladder Cancer

Molecules. 2021 Feb 26;26(5):1253. doi: 10.3390/molecules26051253.

Abstract

Bladder cancer (BC) is the tenth most frequently detected cancer in both sexes. Type-I luteinizing hormone-releasing hormone (LHRH) receptor (LHRH-R-I) is expressed not only in the pituitary, but also in several types of cancer disease. There are few data about LHRH-R-I expression in human BC. This study aimed to investigate the expression of LHRH and LHRH-R-I in the transitional cell carcinoma (TCC) type of human BC. RNA was extracted from 24 human bladder tumor specimens and three BC cell lines. RT-PCR was performed to detect mRNA for LHRH and LHRH-R-I. The protein of LHRH-R-I was further studied by immunohistochemistry (IHC), ligand competition assay, and Western Blot. PCR products of LHRH were found in 19 of 24 (79%) specimens and mRNA of LHRH-R-I was detected in 20 of 24 specimens (83%). Positive immunostaining for LHRH-R-I with different expression intensity was found in all samples examined, showing negative correlation with TCC grade. Radioligand binding studies also showed the presence of specific LHRH-R-I and high affinity binding of LHRH analogs. The high incidence of LHRH-R in BC suggests that it could serve as a molecular target for therapy of human BC with cytotoxic LHRH analogs or modern powerful antagonistic analogs of LHRH.

Keywords: LHRH receptor; RT-PCR; Western Blot; bladder cancer; immunohistochemistry; radioligand binding assay; targeted therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Transitional Cell / drug therapy
  • Carcinoma, Transitional Cell / epidemiology
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gonadotropin-Releasing Hormone / genetics*
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • Receptors, LHRH / genetics*
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / epidemiology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • RNA, Messenger
  • Receptors, LHRH
  • Gonadotropin-Releasing Hormone
  • Doxorubicin