Evidence that involucrin, a marker for differentiation, is oxygen regulated in human squamous cell carcinomas

• Published in: British journal of cancer Vol. 90; no. 3; pp. 728 - 735
• Main Authors: CHOU, S-C, AZUMA, Y, VARIA, M. A, RALEIGH, J. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 09-02-2004
• Subjects: Biological and medical sciences; Biomarkers, Tumor - analysis; Blood vessels; Cancer research; Carcinoma, Squamous Cell - physiopathology; Cell Differentiation; Cell Hypoxia; Cells; Dermatology; Experimental Therapeutics; Female; Head and Neck Neoplasms - physiopathology; Humans; Hypoxia; Kinases; Medical research; Medical sciences; Oxygen - pharmacology; Protein Precursors - metabolism; Proteins; Radiation; Transcription, Genetic; Tumor Cells, Cultured; Tumors of the skin and soft tissue. Premalignant lesions; Uterine Cervical Neoplasms - physiopathology; Human; Imidazole derivatives; Skin disease; Squamous cell carcinoma; Oxygen; Pimonidazole; Biological marker; Environmental factor; Malignant tumor; involucrin; Cell differentiation; Regulation(control); Hypoxia; Differentiation; oxygen regulation
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6601585

The majority of hypoxic cells in squamous cell carcinomas of the head and neck and cervix express involucrin, a molecular marker for differentiation. This raises the question of whether involucrin is an oxygen-regulated protein and, if so, whether it could serve as an endogenous marker for tumour hypoxia. Consistent with oxygen regulation, involucrin protein was found to increase with increasing hypoxia in confluent cultures of moderately differentiated human SCC9 cells. Cells harvested at the point of confluence and exposed to graded concentrations of oxygen revealed a K(m) of approximately 15 mmHg for involucrin induction. This is similar to K(m)s for HIF-1alpha, CAIX and VEGF. Involucrin induction showed a steep dependence on pO(2) with a transition from minimum to maximum expression occurring over less than an order of magnitude change in pO(2). In contrast to SCC9 cells, involucrin was not induced by hypoxia in poorly differentiated SCC4 cells. It is concluded that involucrin is an oxygen-regulated protein, but that differentiation modulates its transcription status with respect to hypoxia induction.