CONSTITUTIVE AND CYTOKINE-INDUCED EXPRESSION OF THE MELANOMA GROWTH-STIMULATORY ACTIVITY GRO-ALPHA GENE REQUIRES BOTH NF-KAPPA-B AND NOVEL CONSTITUTIVE FACTORS
Ld. Wood et A. Richmond, CONSTITUTIVE AND CYTOKINE-INDUCED EXPRESSION OF THE MELANOMA GROWTH-STIMULATORY ACTIVITY GRO-ALPHA GENE REQUIRES BOTH NF-KAPPA-B AND NOVEL CONSTITUTIVE FACTORS, The Journal of biological chemistry, 270(51), 1995, pp. 30619-30626
Melanoma growth stimulatory activity (MGSA)/growth regulated (GRO) and
interleukin-8 (IL-8) are highly related chemokines that have a causal
role in melanoma progression. Expression of these chemokines is simil
ar in that both require the NF-kappa B element and additional regions
such as the CAAT/enhancer binding protein (C/EBP) element of the IL-8
promoter. The constitutive and cytokine IL-1-induced promoter activity
of the chemokine MGSA/GRO alpha in normal retinal pigment epithelial
and the Hs294T melanoma cells is partially regulated through the NF-ka
ppa B element, which binds both NF-kappa B p50 and RelA (NF-kappa B p6
5) homodimers and het erodimers. Mutational analysis of the MGSA/GRO a
lpha promoter reveals that, in addition to the NF-kappa B element, the
immediate upstream region (IUR) is necessary for basal expression in
retinal pigment epithelial and Hs294T cells. Gel mobility shift and UV
cross-linking analyses demonstrate that several constitutive DNA bind
ing proteins interact with the IUR. Although this region has sequence
similarity to the several transcription factor elements including C/EB
P, the IUR includes sequences that have no similarity to previously id
entified enhancer regions. Furthermore, RelA transactivates through ei
ther the NF-kappa B element or the IUR, suggesting a putative interact
ion between NF-kappa B and this novel complex.