Lack of expression of transforming growth factor-β type II receptor associated with malignant progression in human salivary gland cell clones

✍ Scribed by Masayuki Azuma; Tokuyuki Yuki; Tetsuya Tamatani; Katsumi Motegi; Hideo Yoshida; Mitsunobu Sato

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 557 KB
• Volume: 66
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960611)66:6<802::aid-ijc16>3.0.co;2-4

✦ Synopsis

To understand the molecular mechanisms whereby normal human salivary gland cells become malignant and escape growthinhibitory control by transforming growth factor (TGF)-PI, we examined the effect of TGF-P I on the proliferation and expression of TGF-P receptors in cells and the expression of TGF-P type II receptor (TPR-ll) mRNA. An SV40-immortalized normal human salivary gland duct cell clone (NS-SV-DC) with no tumorigenic ability, originally obtained via S.C. implantation into nude mice, was partially resistant to the growth-inhibitory effect of TGF-P I, while a neoplastic human salivary gland duct cell clone (HSGc) with tumorigenic, but not metastatic, potential in nude mice was more resistant to the growth-suppressive effect of TGF-f3 I than NS-SV-DC. Metastatic cell clones derived from carcinogen-treated HSGc were completely refractory to the anti-proliferative effect of TGF-P I. Affinity cross-linking revealed that NS-SV-DC possesses the types I, It (TPR-II) and 111 receptors. However, HSGc and metastatic cell clones lacked expression of detectable levels of the TPR-II protein. Moreover, we evaluated TPR-II mRNA expression in these cell clones by Northern blot analysis and observed that, although NS-SV-DC expressed a large amount of TPR-II mRNA, a small amount of TPR-II mRNA was detectable in HSGc. In contrast, no significant bands were detected in metastatic cell clones. Our results, therefore, suggest that one of the possible mechanisms of escape from autocrine or paracrine growth inhibition by TGF-f3 I during human salivary gland carcinogenesis involves reduced expression or lack of TPR-II.