Disease relevance of SCGB3A1

• CCSP, SCGB3A1, and SCGB3A2 were decreased in airways of neonates with bronchopulmonary dysplasia and in mice after airway injury [1].
• Reintroduction of HIN-1 into breast cancer cells inhibits cell growth [2].
• HIN-1 expression is significantly down regulated in 94% of human breast carcinomas and in 95% of preinvasive lesions, such as ductal and lobular carcinoma in situ [2].
• The HIN-1 gene encoding a small, secreted protein is silenced due to methylation in a substantial fraction of breast, prostate, lung, and pancreatic carcinomas, suggesting a potential tumor suppressor function [3].
• Expression of HIN-1 in synchronized cells inhibits cell cycle reentry and the phosphorylation of the retinoblastoma protein (Rb), whereas in exponentially growing cells, HIN-1 induces apoptosis without apparent cell cycle arrest and effect on Rb phosphorylation [3].

High impact information on SCGB3A1

• HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells [2].
• These results indicate that HIN-1 is a candidate tumor suppressor gene that is inactivated at high frequency in the earliest stages of breast tumorogenesis [2].
• Investigation of multiple signaling pathways revealed that mitogen-induced phosphorylation and activation of AKT are inhibited in HIN-1-expressing cells [3].
• Here, we report that HIN-1 is a potent inhibitor of anchorage-dependent and anchorage-independent cell growth, cell migration, and invasion [3].
• However, analysis of HIN-1 promoter methylation status revealed that in striking contrast to sporadic cases, there is a nearly complete lack of HIN-1 methylation in BRCA1 tumors (P < 0.0001) [4].

Biological context of SCGB3A1

• By searching GenBank expressed sequence tag databases, we identified HIN-2, a protein homologous to HIN-1 [5].
• Down regulation of high in normal-1 (HIN-1) is a frequent event in stage I non-small cell lung cancer and correlates with poor clinical outcome [6].
• The Ugrp2 variant uses a sequence located between authentic exons 1 and 2, resulting in a cytoplasmic form due to a termination codon within the inserted sequence [7].
• Ugrp2 was mapped by fluorescence in situ hybridization to mouse chromosome 11A5-B1 and human chromosome 5q35 [7].
• The expression of HIN-1 is restricted to terminally differentiated airway epithelial cells in vivo and in vitro implicating HIN-1 in the acquisition or maintenance of terminally differentiated epithelial phenotype [8].

Anatomical context of SCGB3A1

• This decrease in HIN-1 expression is accompanied by hypermethylation of its promoter in the majority of breast cancer cell lines (>90%) and primary tumors (74%) [2].
• To establish whether germ-line mutations in HIN-1 may influence breast cancer risk, we sequenced the HIN-1 coding region in 10 familial breast cancer patients with positive logarithm of the odds scores of at least one of the markers flanking HIN-1 [4].
• HIN-1 is highly expressed in the mammary gland, trachea, lung, prostate, pancreas, and salivary gland, and in the lung, its expression is primarily restricted to bronchial epithelial cells [9].
• Methylated HIN-1 promoter was detected in 12 of 26 (46%) nasopharyngeal swabs, 5 of 26 (19%) throat-rinsing fluids, 2 of 11 (18%) plasmas, and 5 of 11 (46%) buffy coats of peripheral blood of the NPC patients but was not detectable in all normal controls [10].

Associations of SCGB3A1 with chemical compounds

• Expression negative cell lines restored HIN-1 expression after treatment with 5-aza-2'-deoxycytidine [11].
• The expression of HIN-1 is up-regulated during retinoic acid induced differentiation of bronchial epithelial cells [8].
• In the presence of PKC inhibitors, D-erythro-sphingosine and OX100, or an inhibitor of MMPs, LU105, allergen-induced migration of LC was strongly decreased [12].

Other interactions of SCGB3A1

• SCGB3A1 messenger RNA localizes to a subset of SCGB3A2-expressing cells within bronchi of both mouse and neonatal human lungs [1].
• The three most frequently methylated genes among this subtype were SCGB3A1 (54%), RASSF1A (29%), and HOXA9 (26%) [13].
• In conclusion, this study has identified several novel epigenetically deregulated target genes in TGCT development, including homeobox genes and SCGB3A1, suggesting that epigenetic inactivation of key genes in normal development also has an important role in TGCTs [13].
• Compared with the primary breast carcinomas, all five genes had higher methylation frequencies in the bone, brain, and lung metastasis, with HIN-1 and RAR-beta methylation being significantly higher (P < 0.01) in each group [14].
• Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors [15].

Analytical, diagnostic and therapeutic context of SCGB3A1

• Expression of HIN-1 mRNA was analyzed by in situ hybridization and quantitative reverse transcribed PCR [16].
• Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between HIN-1 expression and both overall survival (P = 0.0095) and disease-free survival (P = 0.0122) [6].
• In this report, we show that, correlating with the secretory nature of HIN-1, high levels of HIN-1 protein are detected in bronchial lavage, saliva, plasma, and serum [9].

References