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Production of transforming growth factor. cap alpha. in human pancreatic cancer cells: evidence for a superagonist autocrine cycle

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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Previous work showed that cultured human pancreatic cancer cells overexpress the epidermal growth factor (EGF) receptor. In the present study, the authors sought to determine whether some of these cell lines produce transforming growth factor ..cap alpha.. (TGF-..cap alpha..). Utilizing a radiolabeled TGF-..cap alpha.. cDNA in hybridization experiments, they determined that ASPC-1, T/sub 3/M/sub 4/, PANC-1, COLO-357, and MIA PaCa-2 cell lines expressed TGF-..cap alpha.. mRNA. Serum-free medium conditioned by T/sub 3/M/sub 4/ and ASPC-1 cells contained significant amounts of TGF-..cap alpha.. protein. Although unlabeled TGF-..cap alpha.. readily competed with /sup 125/I-labeled EGF for binding, each cell line exhibited lower surface binding and internalization of /sup 125/I-labeled TGF-..cap alpha.. as compared to /sup 125/I-labeled EGF. Both TGF-..cap alpha.. and EGF significantly enhanced the anchorage-independent growth of PANC-1, T/sub 3/M/sub 4/, and ASPC-1 cells. However, TGF-..cap alpha.. was 10- to 100-fold more potent than EGF. These findings suggest that the concomitant overexpression of EGF receptors and production of TGF-..cap alpha.. may represent an efficient mechanism for certain cancer cells to obtain a growth advantage.
Research Organization:
Univ. of Arizona Health Sciences Center, Tucson (USA)
OSTI ID:
6924088
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:21; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550301 -- Cytology-- Tracer Techniques
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
ENDOCRINE GLANDS
GLANDS
GROWTH FACTORS
HYBRIDIZATION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
MAMMALS
MAN
MEMBRANE PROTEINS
MITOGENS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PRIMATES
PROTEINS
RADIOASSAY
RADIOISOTOPES
RECEPTORS
RECOMBINANT DNA
RNA
TUMOR CELLS
VERTEBRATES