Cellular retinol-binding protein 1 (CRBP1)

Cellular retinol-binding protein (CRBP)
Retinol-binding protein 1 (RBP1)
Retinol-binding protein, cellular (RBPC)
RBP1 (gene locus)

Gene: RBP1 maps to 3q21-q22 (Rocchi M. et al., 1989). The gene contains 4 exons encoding 24, 59, 33, and 16 amino acid residues, respectively. The second intron alone occupies 19 kb of the 21 kb of the CRBP gene. The promoter of the gene resembles those found in the 'housekeeping' genes in that it is (G + C)-rich, contains multiple copies of the CCGCCC sequence and lacks TATA box (Nilsson M.L.H. et al., 1988).
mRNA: size:
Protein: CRBP is an acidic protein with a molecular mass of 15.7 kD

Cell lines:
- The concentration of cellular retinol-binding protein (CRBP) was determined in samples of normal and neoplastic mammary gland, using a specific and sensitive radioimmunoassay. The CRBP concentration was significantly higher in neoplastic tissue, but detectable levels were also present in all samples of normal gland. Tubulo-ductal cancers had significantly lower CRBP levels than other cancer types. The CRBP concentration of the neoplastic tissue showed no correlation with the concentration of progesterone or estrogen receptor (Fex G. et al., 1985).

- In 5 breast cancer cell (BCC) lines, T47D, MCF-7, ZR75-1, MDA-MB-231, and BT20, the expression of CRBP1 and the retinoic acid (RA) receptors (RARs) alpha2, beta2, and gamma2 was low or undetectable, and was seldom responsive to 24 h treatment with 1 microM all-trans or 9-cis RA (Northern blot analysis). On the other hand, normal human breast epithelial cells expressed CRBPI and RARbeta2 at the mRNA level, suggesting that loss of expression of these genes is tied to malignant transformation. RARbeta2, but not CRBPI, was also expressed in RA-treated MTSV1-7 cells, an immortalized but nontumorigenic luminal epithelial cell line. Lack of CRBPI and RARbeta2 expression in cancer cells was not due to general impairment of RA signaling, as shown by RA activation of a RARE3-tk-CAT reporter in a subclone of MDA-MB-231 cells that did not express either CRBPI or RARbeta2 (Jing Y. et al., 1996).

Tumors:
- CRBP expression was evaluated by in situ hybridization in six reduction mammoplasty specimens and 49 human breast carcinoma specimens by use of digoxigenin-labeled RNA probes and in nine cultured mammoplasty specimens by northern or western blot analysis. CRBP was expressed in all 15 mammoplasty specimens (normal breast tissue) and in 33 of 35 available specimens of normal tissue adjacent to carcinoma. In contrast, 12 (24%) of 49 carcinoma lesions were uniformly negative for CRBP (P =.023 for comparison with adjacent normal breast tissue). The loss of CRBP expression was as frequent in ductal carcinoma in situ (six [27%] of 22) as in invasive lesions (six [22%] of 27), suggesting that it is a relatively early event in carcinogenesis and not associated with patient age, tumor grade, and expression of steroid receptors or c-Myc. Preliminary experiments did not find an association between CRBP and retinoic acid receptor beta loss, but most (four of five) CRBP-negative tumors were also retinoic acid receptor beta negative (Kuppumbatti Y.S. et al., 2000).

Colantuoni V. et al. (1986) Mapping of human cellular retinol-binding protein to chromosome 3. Cytogenet. Cell Genet. 43: 221-222. (PubMed)
Fex G. et al. (1985) Cellular retinol-binding protein in normal and neoplastic human mammary gland. (PubMed)
Jing Y. et al. (1996) Defective expression of cellular retinol binding protein type I and retinoic acid receptors alpha2, beta2, and gamma2 in human breast cancer cells. FASEB J. 10, 1064-1070. (PubMed)
Kuppumbatti Y.S. et al. (2000) Cellular retinol-binding protein expression and breast cancer. J. Natl. Cancer Inst. 92, 475-480. (PubMed)
Nilsson M.H.L. et al. (1988) Human cellular retinol-binding protein gene organization and chromosomal location. Europ. J. Biochem. 173: 35-44. (PubMed)
Rocchi M. et al. (1989) Regional mapping of RBP4 to 10q23-q24 and RBP1 to 3q21-q22 in man. Somat. Cell Molec. Genet. 15, 185-190. (PubMed)

UniGene data (Hs.101850)