STRUCTURE, EXPRESSION OF PEPTIDE HORMONE GENES IN HUMAN SMALL CELL LUNG CARCINOMA

许多人小细胞肺癌细胞选择性表达肽 在患者和组织培养细胞系中的激素来源于 活检标本。 在患者中，已知这些激素介导 内分泌和神经系统症状的集合， 副肿瘤综合征 其中两种肽，精氨酸加压素 (AVP)和胃泌素释放肽（GRP）被证明是有丝分裂原， Swiss 3T3细胞在某些体外生长条件下。 此外，本发明还提供了一种方法， 单克隆抗血清识别的五个COOH氨基酸残基的 27个氨基酸的GRP激素已被证明可以减缓 SCLS细胞在培养物和裸鼠异种移植物中生长。 采取 总之，这些结果暗示GRP作为一种自分泌生长调节剂， 小细胞肿瘤 为了更好地理解 肽激素基因选择性表达及其生物学作用 在生长调节方面，我们的小组正在推导重组DNA克隆， 相关的多蛋白基因，并使用这些克隆来详细描述它们的基因 结构和表达。 人AVP基因座 在过去的一年里，我们已经获得了AVP的人类基因组克隆， 催产素（OT）基因的结构和核苷酸序列。 这两个结构相似的基因在人类基因组DNA中相连， 位于彼此的10 Kb内，并且在转录水平上相反， 导向 这两个基因在结构上的相似之处 表明它们都是从一个共同的祖先多蛋白基因进化而来的， 重复和倒置。 尽管有类似的结构和位置， AVP和OT基因，人SCLSC细胞系（H378）选择性地 转录AVP而不是OT。 这种选择性的分子基础 目前正在调查中。

Many human small cell lung cancer cells selectively express peptide hormones both in the patient and in tissue culture cell lines derived from biopsy specimens. In patients, these hormones are known to mediate a constellation of endocrine and neurologic symptoms referred to as paraneoplastic syndromes. Two of these peptides, arginine vasopressin (AVP) and gastrin releasing peptide (GRP) are demonstrated mitogens for Swiss 3T3 cells under certain in vitro growth conditions. In addition, monoclonal antisera recognizing the five COOH amino acid residues of the twenty-seven amino acid GRP hormone have been shown to slow the growth of SCLS cells growing in culture and in nude mouse xenografts. Taken together, these results implicate GRP as an autocrine growth regulator of small cell tumors. To better understand the molecular mechanisms governing the selective expression of peptide hormone genes and their biological role in growth regulation, our group is deriving recombinant DNA clones for relevant polyprotein genes and using these clones to detail their gene structure and expression in SCLC. Human AVP Locus Within the last year, we have obtained human genomic clones for AVP and oxytocin (OT) genes an determined their structure and nucleotide sequence. These two structurally similar genes are linked in human genomic DNA, residing within 10 Kb of each other and in opposite transcriptional orientation. The parallels in structure between these two genes strongly suggests that they both evolved from a common ancestral polyprotein gene by duplication and inversion. Despite the similar structure and location of the AVP and OT genes, a human SCLSC cell line (H378) selectively transcribes AVP and not OT. The molecular basis for this selective expression is currently under investigation.