Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer.
OBJECTIVE
Small cell lung cancer (SCLC) is a rapidly growing neoplasm accounting for approximately 20% of patients with lung cancer. Progastrin-releasing peptide (proGRP) is produced in about two-thirds of SCLC tumors and is used as a specific marker for SCLC. Although GRP is known to have a variety of biological functions, only limited information is available concerning expression of proGRP mRNA and protein, and that of the receptor for GRP (GRPR) in SCLC tumors.


METHODS
In individuals with SCLC, the levels of serum proGRP(31-98) were measured by enzyme-linked immunosorbent assay. Expression of proGRP as well as GRPR mRNA in SCLC tumor tissues was investigated by reverse transcription-nested polymerase chain reaction (PCR) amplification. The proportions of alternatively spliced proGRP mRNA transcripts were analyzed in proGRP-producing tumors by nested and competitive PCR amplification. Finally, production of proGRP protein in SCLC tumor was evaluated by using immunohistochemical staining with a polyclonal human anti-proGRP antibody.


RESULTS
ProGRP mRNA transcripts could be detected only in tumor tissues recovered from individuals with high serum proGRP levels. The proportions of mRNA subtypes in each case were nearly the same, revealing type I of 55.4+/-7.6%, type II with 21-b deletion of 1.8+/-3.6%, and type III with 19-b deletion of 42.8+/-4.3%, respectively. ProGRP protein production was demonstrated in tumor tissues exclusively from individuals exhibiting high serum proGRP levels. In contrast, GRPR mRNA transcripts were detectable in cancer cells from two of five proGRP-expressing tumor tissues.


CONCLUSIONS
ProGRP mRNA expression is closely related with the synthesis of proGRP protein which is eventually released into the blood. It is suggested GRP may function as an autocrine growth factor for cancer cells in a subgroup of SCLC patients through, at least in part, upregulation of GRPR expression.
Uchida
Kazuhiro
K
Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Kojima
Akira
A
Morokawa
Nasa
N
Tanabe
Osamu
O
Anzai
Chieko
C
Kawakami
Makio
M
Eto
Yoshikatsu
Y
Yoshimura
Kunihiko
K
D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics*; D010455:Peptides / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D018004:Receptors, Bombesin / Q000097:blood / Q000235:genetics*; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D017931:DNA Primers; D018076:DNA, Complementary; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D011994:Recombinant Proteins; C087079:pro-gastrin-releasing peptide (31-98)