Faculty Collaboration Database

Alterations in transforming growth factor-alpha and epidermal growth factor receptor expression during rat esophageal tumorigenesis. Mol Carcinog 1996 Feb;15(2):144-53

Date

02/01/1996

Pubmed ID

8599581

DOI

10.1002/(SICI)1098-2744(199602)15:2<144::AID-MC7>3.0.CO;2-J

Scopus ID

2-s2.0-0029917811 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

Transforming growth factor-alpha (TGF-alpha) stimulates cell proliferation through interaction with its receptor, the epidermal growth factor receptor (EGFR), by activating its tyrosine kinase activities. The simultaneous overexpression of TGF-alpha and EGFR by tumor cells is thought to trigger the autocrine growth pathway, leading to uncontrolled proliferation. To examine their roles in rat esophageal tumorigenesis induced by the chemical carcinogen N-nitrosomethylbenzylamine (NMBA), TGF-alpha, and EGFR expression was evaluated in normal rat esophageal epithelium, in NMBA-induced preneoplastic lesions, and in papillomas by quantitative reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemical analyses. Compared with the levels in normal epithelium, the TGF-alpha and EGFR mRNA levels in esophageal papillomas were 3.6 and 1.9 times higher, respectively. In the preneoplastic epithelium, although a trend of increased TGF-alpha and EGFR mRNA levels was observed, collectively there were no significant differences between preneoplastic and normal samples by RT-PCR analysis. In situ hybridization and immunohistochemical staining showed increased levels of TGF-alpha and EGFR mRNA and protein products in papillomas and in pronounced hyperplastic and dysplastic lesions. TGF-alpha and EGFR expression correlated with each other and with the expression of proliferating cell nuclear antigen, a marker for cell proliferation. These results suggest that disregulation of TGF-alpha and EGFR expression may contribute to autonomous cell growth and may play an important role in rat esophageal tumorigenesis induced by NMBA.

Author List

Wang QS, Sabourin CL, Bijur GN, Robertson FM, Stoner GD

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Carcinogens
Cell Division
Cell Transformation, Neoplastic
DNA Primers
Dimethylnitrosamine
ErbB Receptors
Esophageal Neoplasms
Esophagus
Gene Expression
In Situ Hybridization
Male
Molecular Sequence Data
Papilloma
Polymerase Chain Reaction
Precancerous Conditions
RNA, Messenger
Rats
Rats, Inbred F344