Non-small cell lung cancer - Homo sapiens (human)

Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heterogeneous group of cancers, consisting mainly of squamous cell (SCC), adeno (AC) and large-cell carcinoma. Molecular mechanisms altered in NSCLC include activation of oncogenes, such as K-RAS and c-erbB-2, and inactivation of tumorsuppressor genes, such as p53, p16INK4a, RAR-beta, and RASSF1. Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. Overexpression of c-erbB-2 or EGFR leads to a proliferative advantage. Inactivating mutation of p53 can lead to more rapid proliferation and reduced apoptosis. The protein encoded by the p16INK4a  inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. Loss of p16INK4a expression is a common feature of NSCLC. RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. RASSF1A is able to form heterodimers with Nore-1, an RAS effector.Therefore loss of RASSF1A might shift the balance of RAS activity towards a growth-promoting effect.

Human Diseases; Cancers

Homo sapiens (human) [GN:hsa]

PMID:12379883

Osada H, Takahashi T.

Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer.

Oncogene 21:7421-34 (2002)

PMID:12741677

Yokota J, Nishioka M, Tani M, Kohno T.

Genetic alterations responsible for metastatic phenotypes of lung cancer cells.

Clin Exp Metastasis 20:189-93 (2003)

PMID:16870043

Aviel-Ronen S, Blackhall FH, Shepherd FA, Tsao MS.

K-ras mutations in non-small-cell lung carcinoma: a review.

Clin Lung Cancer 8:30-8 (2006)

PMID:15948711

Pfeifer GP, Dammann R.

Methylation of the tumor suppressor gene RASSF1A in human tumors.

Biochemistry (Mosc) 70:576-83 (2005)

PMID:11902573

Altucci L, Gronemeyer H.

The promise of retinoids to fight against cancer.

Nat Rev Cancer 1:181-93 (2001)

PMID:10944551

Virmani AK, Rathi A, Zochbauer-Muller S, Sacchi N, Fukuyama Y, Bryant D, Maitra A, Heda S, Fong KM, Thunnissen F, Minna JD, Gazdar AF.

Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas.

J Natl Cancer Inst 92:1303-7 (2000)

PMID:12867060

Hirsch FR, Scagliotti GV, Langer CJ, Varella-Garcia M, Franklin WA.

Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies.

Lung Cancer 41 Suppl 1:S29-42 (2003)

PMID:16112428

Panani AD, Roussos C.

Cytogenetic and molecular aspects of lung cancer.

Cancer Lett 239:1-9 (2006)

PMID:12407699

Mitsuuchi Y, Testa JR.

Cytogenetics and molecular genetics of lung cancer.

Am J Med Genet 115:183-8 (2002)

PMID:15942304

Breuer RH, Postmus PE, Smit EF.

Molecular pathology of non-small-cell lung cancer.

Respiration 72:313-30 (2005)

PMID:11895903

Piyathilake CJ, Frost AR, Manne U, Weiss H, Bell WC, Heimburger DC, Grizzle WE.

Differential expression of growth factors in squamous cell carcinoma and precancerous lesions of the lung.

Clin Cancer Res 8:734-44 (2002)

PMID:16189154

Awaya H, Takeshima Y, Furonaka O, Kohno N, Inai K.

Gene amplification and protein expression of EGFR and HER2 by chromogenic in situ hybridisation and immunohistochemistry in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

J Clin Pathol 58:1076-80 (2005)