SECRETOGLOBIN, FAMILY 3A, MEMBER 1; SCGB3A1

Alternative titles; symbols

• UTEROGLOBIN-RELATED PROTEIN 2; UGRP2
• HIN1

HGNC Approved Gene Symbol: SCGB3A1

Cytogenetic location: 5q35.3 Genomic coordinates (GRCh38): 5:180,590,104-180,591,498 (from NCBI)

▼ Description
Members of the secretoglobin family, such as SCGB3A1, are secreted proteins of about 10 kD that are found in high concentrations in fluids of lung, lacrimal gland, salivary gland, prostate, uterus, and other tissues. Secretoglobins form stable dimers prior to secretion (summary by Jackson et al., 2011).

▼ Cloning and Expression
Breast cancer progresses from atypical hyperproliferation to in situ and then invasive carcinomas before culminating in metastatic disease. Ductal carcinoma in situ (DCIS) is thought to be the precursor of invasive ductal carcinoma. Using SAGE (serial analysis of gene expression) of normal and DCIS luminal mammary epithelium tissue, Krop et al. (2001) isolated a cDNA encoding HIN1 (high in normal-1), so named because it was highly expressed in normal breast tissue but absent in 90 other normal and cancerous tissue types. The deduced 104-amino acid HIN1 protein contains a signal peptide and is conserved in several species. Northern blot and RT-PCR analyses revealed HIN1 expression in normal breast luminal tissue, but not in myoepithelial cells or breast cancer cell lines. HIN1 was highly expressed in breast tissue from a woman in the twenty-fifth week of pregnancy. In situ hybridization analysis confirmed the expression of HIN1 in small ducts and lobules, irrespective of their proliferation and hormone receptor status. HIN1 was also highly expressed in other tissues with branching ductal epithelia. No expression was detected in large or DCIS ducts. Western blot analysis showed expression of an 8-kD protein.

Reynolds et al. (2002) found that, in neonatal human lung tissue, SCGB3A1 was expressed predominantly in large airways and midlevel bronchus. SCGB3A1 appeared to be expressed in cells distinct from those expressing SCGB3A2 (606531). In submucosal gland, SCGB3A1 was expressed in both acinar and ductile cells. Little to no SCGB3A1 or SCGB3A2 expression was detected in upper airway epithelium in lung tissue from human neonates that died of bronchopulmonary dysplasia, but expression in submucosal glands and ducts was similar to normal controls.

▼ Gene Function
Krop et al. (2001) determined by sequence analysis of bisulfite-treated genomic DNA and by PCR that hypermethylation of CpGs occurs in the HIN1 promoter in most cancerous breast tissue, but not in normal breast tissue. HIN1 expression significantly decreased colony numbers in an invasive ductal tumor cell line, but less so in ductal carcinoma cells; the decrease was less than that caused by p53 (191170) expression in either line. Krop et al. (2001) concluded that HIN1 is a candidate tumor suppressor gene and a putative growth inhibitory cytokine, possibly acting in a concentration-dependent autocrine manner. They also suggested that HIN1 is an excellent marker for early detection of breast cancer.

▼ Mapping
By FISH, Krop et al. (2001) mapped the HIN1 gene to 5q35-tel, a region not previously implicated in breast cancer. However, loss of heterozygosity of 5q is frequent in other carcinomas.

▼ Evolution
Jackson et al. (2011) noted that humans have 11 SCGB genes and 5 pseudogenes, whereas mice have 68 Scgb genes. Only 4 human genes have direct mouse orthologs: SCGB1A1 (192020), SCGB1C1 (610176), SCGB3A1, and SCGB3A2 (606531).