TY - JOUR

T1 - Peptide hormone processing in tumours

T2 - Biogenetic and diagnostic implications

AU - Rehfeld, J. F.

AU - Bardram, L.

AU - Blanke, S.

AU - Bundgaard, J. R.

AU - Friis-Hansen, L.

AU - Hilsted, L.

AU - Johnsen, A. H.

AU - Kofod, M.

AU - Lultichau, H. R.

AU - Monstein, H. J.

AU - Nielsen, C.

AU - Nielsen, F. C.

AU - Paloheimc, L. I.

AU - Pedersen, K.

AU - Pildal, J.

AU - Ramlau, J.

AU - Van Solinge, W. W.

AU - Thorup, U.

AU - Ødum, L.

PY - 1993

Y1 - 1993

N2 - Insight into the biogenesis of peptide hormones has grown explosively by elucidation of gene, mRNA and prohormone structures. In addition, information about prohormone processing enzymes is rapidly accumulating. Prohormones vary in size and organization from poly- to monoprotcin structures. According to their structural organization and sequence homology. hormones are grouped in families. Prohormones are processed to bioactive peptides by multiple modifications during the transport from the endoplasmic reticulum to secretory granules. The modifications comprise different proteolytic cleavages and amino acid dcri vatizations. By constitutive secretion, the processing is less pronounced. The same prohormone may be expressed in several cell types that process the precursor in different ways. Awareness of cell-specific processing patterns is important for understanding the tumour synthesis of peptides and for appropriate diagnosis of peptidc-producing tumours. These tumours comprise not only well-known neuroendocrine neoplasias. An increasing number of common carcinomas also expresses peptide hormone genes. However, the translation and post-translational processing in tumours are generally attenuated. Consequently. the expression is often functionally and clinically silent. A new diagnostic tool, processing-independent analysis (PI A), seems promising in quantitation of hormone gene expression at peptide level irrespective of the degree of processing. Studies of progastrin expression and processing in tumours illustrate the diagnostic superiority of PIA.

AB - Insight into the biogenesis of peptide hormones has grown explosively by elucidation of gene, mRNA and prohormone structures. In addition, information about prohormone processing enzymes is rapidly accumulating. Prohormones vary in size and organization from poly- to monoprotcin structures. According to their structural organization and sequence homology. hormones are grouped in families. Prohormones are processed to bioactive peptides by multiple modifications during the transport from the endoplasmic reticulum to secretory granules. The modifications comprise different proteolytic cleavages and amino acid dcri vatizations. By constitutive secretion, the processing is less pronounced. The same prohormone may be expressed in several cell types that process the precursor in different ways. Awareness of cell-specific processing patterns is important for understanding the tumour synthesis of peptides and for appropriate diagnosis of peptidc-producing tumours. These tumours comprise not only well-known neuroendocrine neoplasias. An increasing number of common carcinomas also expresses peptide hormone genes. However, the translation and post-translational processing in tumours are generally attenuated. Consequently. the expression is often functionally and clinically silent. A new diagnostic tool, processing-independent analysis (PI A), seems promising in quantitation of hormone gene expression at peptide level irrespective of the degree of processing. Studies of progastrin expression and processing in tumours illustrate the diagnostic superiority of PIA.

KW - Biogenesis

KW - Hormone genes

KW - Hormone-producing tumours

KW - Peptide hormones

KW - Precursors

KW - Processing-independent analysis

UR - http://www.scopus.com/inward/record.url?scp=0027483946&partnerID=8YFLogxK

U2 - 10.1159/000217833

DO - 10.1159/000217833

M3 - Journal article

C2 - 8210950

AN - SCOPUS:0027483946

VL - 14

SP - 174

EP - 183

JO - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 3

ER -